Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.
These finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.
However, cell treatment with the ferroptosis inhibitor, ferrostatin‑1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2‑induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.
This study reported that the DNA topoisomerase II (Topo II) inhibitors, doxorubicin and etoposide (VP-16) synergistically decreased cell survival with enhanced induction of DNA damage and apoptosis in osimertinib-resistant cells, suppressed the growth of osimertinib-resistant tumors, and delayed the emergence of osimertinib acquired resistance. Enforced expression of an ectopic TOP2A gene in sensitive EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their response to undergo osimertinib-induced DNA damage and apoptosis. Together, these results reveal an essential role of Topo IIα inhibition in mediating the therapeutic efficacy of osimertinib against EGFRm NSCLC, providing scientific rationale for targeting Topo II to manage acquired resistance to osimertinib.
It is demonstrated that circZCCHC2 plays a crucial role in the malignant progression of TNBC via the miR-1200/TPR axis, thereby activating the RAS-RAF-MEK-ERK pathway. The present results indicate that circZCCHC2 has the potential to serve as a novel prognostic biomarker for TNBC.
The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.
R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting.
The design of the novel liposomal L-annamycin (L-ANN) was the replacement of a basic amine at the C-3' position with a hydroxy group, which was shown to significantly reduce cardiotoxicity when compared with doxorubicin...All patients will also receive cytarabine 2... Initial data suggested that L-ANN is safe and active in heavily pretreated r/r AML patients with no signs of cardiotoxicity. This study is currently being conducted in Europe across 5 sites in Poland and 3 in Italy. Results from the Phase 2 portion of this study will be presented at the meeting.
AST can inhibit H9c2 apoptosis induced by THP and attenuate H9c2 damage by THP, which may be achieved by downregulating miR-494-3p, upregulating MDM4, and inhibiting p53.
7 months ago
Journal
|
MDM4 (The mouse double minute 4) • MIR494 (MicroRNA 494)
Knockdown of miR-129-1-3p reversed the protective effect of Miat knockdown on HL-1. Miat knockdown can alleviate THP-induced cardiomyocyte injury by regulating miR-129-1-3p.
Recurrent chromosomal translocations in the therapy-related leukemia differ from chromosomal rearrangements associated with other neoplasias. Here, we reviewed the factors that drive chromosomal translocations induced by cancer treatment with DNA topoisomerase II inhibitors, such as mobility of ends of double-strand DNA breaks formed before the translocation and gain of function of fusion proteins generated as a result of translocation.
Treatment with VIP236 resulted in long-lasting tumor regression in subcutaneous patient-derived xenograft (PDX) models from patients with non-small-cell lung, colon, and renal cancer as well as in two orthotopic metastatic triple-negative breast cancer PDX models. In these models, a significant reduction of brain and lung metastases also was observed.
In summary, PEG-[Irinotecan] displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan. This supports the view that PEG-[Irinotecan] is a superior anticancer drug to irinotecan and it has entered the phase II trial stage.
Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of Mitomycin and BCG on recurrence rates.
This may be related to the reduction of calcium ions in 4T1. In conclusion, Miat knockdown enhanced the sensitivity of THP to 4T1 by inhibiting calcium channels.
Describing CBP-1008: a FR/ TRPV6 targeted drug conjugate in Phase II pivotal studies of advanced ovarian cancer treatment; Exploring CBP-1018: a FR/ PSMA targeted drug conjugate in Phase Ib for prostate cancer therapy; Highlighting CBP-1019: TOP1i payload drug conjugate for unmet medical needs
9 months ago
Clinical
|
TRPV6 (Transient Receptor Potential Cation Channel Subfamily V Member 6)
Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome.
The residues ASP96, GLN100, PRO184, and THR185 of compound cefpiramide, doxycycline, delafloxacin, metacycline, oxytetracycline, and ertapenem were involved in the binding with CagA protein. These residues are crucial for the CagA that aids in entry or pathogenesis of the bacterium. The screened FDA-approved antibiotics have a potential druggability to inhibit CagA and reduce the progression of H. pylori borne diseases.
Silencing circEGFR inhibited the malignant progression of the tumor. These results revealed circEGFR is a promising biomarker for TNBC diagnosis, therapeutic and prognosis.
In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs...Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.
Preoperative intravesical instillation of THP is conducive to identifying suspicious lesions. The combination of a 980-nm laser with preoperative THP intravesical instillation can significantly prolong RFS time.
P2, N=50, Recruiting, Sun Yat-sen University | Unknown status --> Recruiting | Trial completion date: Mar 2021 --> Mar 2025 | Trial primary completion date: Mar 2021 --> Mar 2025
11 months ago
Enrollment open • Trial completion date • Trial primary completion date
Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.
To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L-Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia.
Aspirin, which is an AKR1C1 inhibitor, could help reduce the drug resistance caused by AKR1C1. After receiving THP treatment, the bladder cancer cell lines could upregulate the expression of the AKR1C1 gene through the ROS/KEAP1/NRF2 pathway, leading to resistance to THP treatment. Using tempol, which is an inhibitor of ROS, could prevent the upregulation of AKR1C1 expression.
The antibody-drug conjugate (ADC) ABBV-400 consists of the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor (Top1i) payload. On the basis of DLTs, a maximum tolerated dose of ABBV-400 was identified. At this dose, safety results appear comparable with other Top1i ADCs. Promising antitumor activity was seen with ABBV-400 across tumor types, justifying further evaluation in the ongoing dose expansion in NSCLC, GEA, and CRC.
The efficacies of DEB-TACE loaded with pirarubicin, raltitrexed, or arsenic trioxide in treating HCC were generally comparable, and the survival benefit of patients was similar. The short-term efficacy of the pirarubicin group and arsenic trioxide group was slightly better than that of the raltitrexed group.
In summary, VIP236 monotherapy efficacy in NSCLC, gastric, TNBC, RCC, CRC, and metastatic TNBC in vivo cancer models provides a rationale for clinical investigation in advanced metastatic solid tumors. In gastric cancer, VIP236 showed improved efficacy compared with the approved ADC, trastuzumab deruxtecan, regardless of HER2 expression. These results warrant further evaluation in clinical trials.
GLP toxicity studies using cynomolgus monkeys showed that YL202 is well tolerated with calculated therapeutic index (TI, HNSTD/MED) of ~100 for repeat dosing. No lung or platelet toxicity findings were observed at doses up to the maximum tolerated dose (MTD).Based on these preclinical results, it demonstrates that YL202’s advanced ADC design results in an increased therapeutic margin, and YL201 could be further developed in HER3 positive cancer patients.
The patient received R-THP-COP therapy which consisted of rituximab, pirarubicin, cyclophosphamide, vincristine and prednisolone. After four chemotherapy courses, a partial response according to the the response evaluation criteria in solid tumors was obtained. The patient was discharged with no signs of recurrence.
The killing assay showed that these primary breast cancer cells responded differently to doxorubicin and pirarubicin treatment. These results indicate that our established primary breast cancer cell model holds great promise for predicting breast cancer sensitivity to chemotherapy drugs.
Thirty pts will be enrolled and received 5 cycles of anlotinib (12 mg qd, d1-14; 21 days per cycle) plus 6 cycles of nab-paclitaxel (200 mg/m2, once every 3 weeks), anthracycline ( pirarubicin 50 mg/m2) and cyclophosphamide at 500 mg/m2, followed by surgery. The trail is in progress.