BCL2 (B-cell CLL/lymphoma 2)

P1, N=9, Active, not recruiting, Wugen, Inc. | Trial completion date: Dec 2025 --> Jan 2025

Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone...Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells. These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

This study revealed the involvement of PGAM1 in the aerobic glycolysis of melanoma, providing novel insights into the molecular mechanisms of melanoma progression.

Subsequently, up-regulated β-catenin partially counteracted the effects of miR-139-5p in BMSC-exos on AML cell proliferation and apoptosis. BMSC-exos targeted to repress β-catenin expression by miR-139-5p, limited AML cell proliferation and facilitated apoptosis.

The protein expression of phosphorylated-Akt and phosphorylated-CREB, essential genes in neuroplasticity, was also increased in cells treated with H2O2 and MO. Therefore, the neuroprotective effects of MO against oxidative stress are attributed to its antioxidant and antiapoptotic properties, as well as its ability to modify the neuronal signaling pathway.

The docking study showed that compounds 22 and 29 had docking scores similar to those of Erlotinib and Sorafenib, co-crystallized ligands, for the EGFR and VEGFR-2 proteins. The experiments on lipophilicity showed that the new pyrimidines had a consistent result. This group of compounds has better biological activity in all the biological systems studied with low lipophilicity.

P2, N=132, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2029 --> Mar 2030 | Trial primary completion date: May 2025 --> May 2026

Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.

ARV825, a bromodomain-containing protein 4 (BRD4)-PROTAC, has demonstrated the capacity to enhance the antitumor effect of the classic chemotherapeutic agent docetaxel (DTX)...This, in turn, augmented the antitumor effect of DTX in vivo without undesired side effects. In conclusion, BRD4-PROTAC may serve as a promising synergistic agent alongside the conventional chemotherapeutic agent DTX, with liposomes functioning as effective co-delivery vehicles.

Furthermore, relevant changes were detected in the expression of Bcl-2, BAX, FAS, and BIRC-5, while no significant alteration in the expression of NOXs was observed. In conclusion, our findings suggested that the combination of BrNQ and TA though the ability to change redox status in tumor cells could act as a potential adjuvant treatment modality for improve prognosis in TNBC.

Overall, APE exhibits anti-tumor effects on NSCLC via induction of apoptosis, attenuation of EMT, and its mechanism involves the suppression of the PI3K/Akt pathway. Our study offers new insights for the identification of novel drug development for NSCLC.

Moreover, 4a increased reactive oxygen species (ROS) levels in KYSE 30 cells and upregulated the expression of proteins related to the ROS related MAPK signaling pathway (p-ERK, p-p38, and p-JNK). These findings suggest that compound 4a holds promising potential as an antiproliferative agent by targeting MAPK signaling pathway to inhibit cell cycle progress, induce apoptosis and produce ROS in cancers.

Sorafenib, Temozolomide, U-73122, and LOXO-101 effectively eliminate cancer cells. Inhibiting the pathways regulated by TrkB receptor combined with Temozolomide action, led to successful gliomas elimination. Those results might serve as basis for modern targeted treatment development.

We identified a distinct high-risk DLBCL subgroup, characterized by MYC and BCL2 aberrations, beyond conventional DHL-BCL2 and DEL, and irrespective of cell-of-origin, thereby expanding the poor-prognosis group.

The findings of the current study demonstrated that the simultaneous consumption of a certain amount of broccoli extract and SI can be considered as a promising therapeutic strategy for treatment of endometriosis.

After Rap treatment, both autophagy and apoptosis of CTD-induced L-O2 cells were significantly enhanced. The molecular mechanism of CTD-induced toxicity in mouse liver and L-O2 cells is mainly through DDIT4/mTOR signaling pathway activation, leading to an increase in autophagy and apoptosis levels.

The potential pharmacological mechanism of BZYQ in treating CRF, as predicted by network pharmacology, offers a molecular foundation for clinical CRF treatment. https://inplasy.com, identifier INPLASY202430025.

Furthermore, C6 induced DNA damage by down-regulating the expression of thymidylate synthase. These results indicated that C6 is a potential antitumor agent and kills HCT-116 cells through DNA damage, mitochondrial dysfunction, and oxidative stress.

These findings suggest that melatonin can diminish lung tissue damage, apoptosis, and inflammatory responses induced by passive smoking, as well as decrease the expression of lung cancer-related genes. Further experimental investigations involving exogenous melatonin treatments will be needed.

P1/2, N=56, Not yet recruiting, BeiGene

Mechanistically, Rg3 attenuates the stemness of BCSCs by activating the Hippo signaling pathway. This study provides a comprehensive evaluation of Rg3 as a promising therapeutic agent against BCSCs.

We synthesized F2-C-5-FU conjugates by linking carboxymethyl-5-fluorouracil (C-5-FU) with folic acid (FA) through ester bonding...The treatment promoted cancer cell apoptosis by inhibiting the expression of apoptosis-related proteins. Overall, F2-C-5-FU-FA conjugates demonstrate potential as an effective drug delivery system for targeted colorectal cancer therapy.

We also evaluated the therapeutic potential of targeting these proteins with AZD0466, a novel drug-dendrimer conjugate of the BCL2/-XL inhibitor AZD4320, and with BCL2 inhibitor venetoclax (ABT-199). Our findings therefore suggest that the novel dual BCL2/-XL inhibitor AZD0466 outperforms single BCL2 inhibition by venetoclax in T-ALL. These findings facilitate the translation of dual BCL2/-XL inhibitors into ALL clinical trials, either alone or in combination with standard- of- care chemotherapy and immune therapies.

Among five genes, ALB, ESR1 and SRC tend to be core genes because of probable status as potential targets for sorafenib...Regulating the expression of TanIIA-related gene signatures (ALB, SRC and ESR1), and inhibiting the SRC/MAPK/ERK signaling axis might potentially contribute to the TanIIA treatment of HCC. And the three gene signatures could be identified for predicting the prognosis of HCC, which may provide novel biomarkers for HCC treatment.

P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Sep 2024 --> Sep 2025

The study provides insights into the modulation of key cellular processes, indicating that nsPEF technology could improve the outcomes of conventional cancer treatments through enhanced efficacy and potentially mitigating drug resistance mechanisms. The promising results advocate for further research to optimize nsPEF protocols for clinical application, highlighting the potential of electrical fields in advancing cancer therapy.

Our results suggest that an integrated NGS strategy should not replace FISH or be routinely used in the workup to detect the clinically relevant rearrangements in HGBCL. It may serve as a complement to FISH testing when FISH shows negative results.

After the exogenous addition of GABA, all the above genes have a certain degree of callback, but GH, HSP70, HSP90, IL-1β, Bax, Nrf2, CAT, and SOD have not yet reached the level of the control group. These results indicate that adding GABA to feed can alleviate the adverse effects of combined stress of flow rate and density to a certain extent and provide insights for solving the problems in the circular aquaculture model of largemouth bass.

A dose escalation study in BALB/c mice showed that P-PENT and P-HEX were approximately 5-fold and 4-fold more tolerated than cisplatin, respectively. In conclusion, the present study provides evidence that P-PENT and P-HEX may have the characteristics of an effective and potentially safe anti-tumor drug that could be used in skin cancer treatment.

Dioscin exerts a certain inhibitory effect on HCT116, and its mechanism of action may be linked, with the inhibition of the Notch1 signaling pathway.

The binding affinity values were found to be - 8.7 kcal/mol, - 7.9 kcal/mol, - 9.6 kcal/mol, - 9.5 kcal/mol, - 12 kcal/mol and - 11.1 kcal/mol for BAD, BCl-2, p53, Caspase-8, Caspase-9 and Caspase-3 respectively. Taken together, our synthesized CDs-CeO2 nanohybrid could be thought as a potential anticarcinogenic option in the field of breast cancer therapeutics.

These results show that the drug activity modulates the investigated inflammatory and apoptotic genes in the prostate gland of PCa-induced rats, thus demonstrating its anti-PCa potential. The results of this study suggest the potential of a novel treatment protocol of I. macrophylla plant extract to improve therapeutic outcomes for patients with aggressive PCa, which reportedly claims hundreds of thousands of lives yearly.

Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy. Genetic profiling of the tumors revealed differences in the expression levels of genes associated with TGFβ, epithelial to mesenchymal transition (EMT), TLR-4, and Bcl2 signaling, alluding to the susceptibility to specific gene signatures to the treatment. Taken together, our study suggests that TGFβi and PTX combination therapy using high-capacity POx micelle delivery provides a robust antitumor response in multiple TNBC subtype mouse models.

This review aims to elucidate the primary mechanisms underlying resistance to venetoclax and explore current therapeutic strategies to overcome this challenge.Expert opinion: In patients with venetoclax resistance, alternative options include targeted combination therapies tailored to individual cases based on cytogenetics and prior treatments. Many of these therapies require further clinical investigation to validate their safety and efficacy.

Findings verify for the first time the neuroprotective potential of golden berry leaf, currently discarded as agricultural waste, and highlight its multifaceted mechanism of neuroprotection in CP-induced neurotoxicity, suggesting its suitability as a promising therapeutic agent for neurotoxicity management.

The increased expression of BAX and decreased expression of Bcl-2, MMP-2, and MMP-9 confirmed the pro-apoptotic and anti-metastatic effects of 4-FLC-LNPs. These finding validate the therapeutic potential of 4-FLC-LNPs, which may be utilized in preclinical studies.

The combination of MST-312 and imatinib shows potential as a CML therapy. However, further research and clinical trials are necessary to validate these findings and determine their clinical relevance.

Relapsed/refractory LBCL remains radioresponsive with 60-80% response rate to RT. While DHL pathology does not appear to influence RT response, its presence is associated with higher rates of local recurrence, suggesting it may be more radioresistant.

Collectively, these findings comprehend attributes of herbacetin as an alternative therapeutic strategy in relieving LPS-associated chronic inflammatory disorders.

P1/2, N=54, Completed, Incyte Corporation | Active, not recruiting --> Completed

This case report presents a unique instance of an intracranial dedifferentiated SFT with rhabdomyosarcomatous dedifferentiation, highlighting the significant diagnostic challenges posed by this rare entity.

Transcriptomic and metabolic analysis of primary T-ALL cells next translated our findings to the human pathology, showing that PTEN-altered T-ALL cells activate ACLY and are sensitive to its genetic targeting. ACLY activation thus represents a metabolic vulnerability with therapeutic potential for high-risk T-ALL patients.