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Cancer Medicine Jun 2024The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with...
BACKGROUND
The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib.
METHODS
This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort.
RESULTS
We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS.
CONCLUSIONS
The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Quinolines; Phenylurea Compounds; Male; Female; Middle Aged; Retrospective Studies; Aged; Prognosis; Antineoplastic Agents; Adult
PubMed: 38923354
DOI: 10.1002/cam4.7410 -
Cancer Medicine Jun 2024HER2 is an infrequently mutated driver gene in non-small cell lung cancer (NSCLC). At present, there has been no comprehensive large-scale clinical study to establish...
OBJECTIVES
HER2 is an infrequently mutated driver gene in non-small cell lung cancer (NSCLC). At present, there has been no comprehensive large-scale clinical study to establish the optimal first-line treatment strategy for advanced lung adenocarcinoma (LUAD) with HER2-Mutant. Besides that, the effectiveness and safety of pyrotinib, a pan-HER inhibitor, in the context of NSCLC are still undergoing investigation.
MATERIALS AND METHODS
In this study, we conducted a retrospective data collection of HER2-Mutated advanced LUAD who received first-line treatment and pyrotinib between May 2014 and June 2023. Patients treated with chemotherapy, chemotherapy + immune checkpoint inhibitors (ICIs), chemotherapy + bevacizumab and pyrotinib in first-line treatment. Furthermore, we collected data on the efficacy and safety of pyrotinib in these patients after disease progression. The main endpoint of the study was progression-free survival (PFS).
RESULTS
In the final analysis, 89 patients were included in the first-line cohort and 30 patients were included in the pyrotinib cohort. In the first-line treatment cohort, chemotherapy + ICIs, chemotherapy + bevacizumab, and pyrotinib exhibited notable survival benefits compared to chemotherapy (median PFS: 9.87 vs. 7.77 vs. 7.10 vs. 5.40 months, p-value < 0.05). Furthermore, patients with a first-line treatment PFS of less than 6 months may potentially benefit from subsequent treatment with pyrotinib (median PFS: 7.467 vs. 3.000, p-value = 0.0490).
CONCLUSIONS
In the first-line treatment of HER2-Mutant LUAD, regimens involving combinations like chemotherapy + ICIs, chemotherapy + bevacizumab, and pyrotinib may confer enhanced survival advantages compared to chemotherapy. Nevertheless, no significant distinctions were observed among these three treatment strategies, underscoring the imperative to identify biomarkers for the discerning selection of suitable therapeutic modalities. Moreover, patients with suboptimal response to first-line treatment may potentially derive more benefit from pyrotinib.
Topics: Humans; Female; Retrospective Studies; Male; Middle Aged; Aged; Lung Neoplasms; Receptor, ErbB-2; Mutation; Acrylamides; Adenocarcinoma of Lung; Antineoplastic Combined Chemotherapy Protocols; Progression-Free Survival; Adult; Aminoquinolines; Immune Checkpoint Inhibitors; Bevacizumab; Aged, 80 and over
PubMed: 38923311
DOI: 10.1002/cam4.7335 -
Anais Da Academia Brasileira de Ciencias 2024Klebsiella pneumoniae (K. pneumoniae) is a major cause of healthcare-associated infections and plays a prominent role in the widespread antibiotic resistance crisis....
Klebsiella pneumoniae (K. pneumoniae) is a major cause of healthcare-associated infections and plays a prominent role in the widespread antibiotic resistance crisis. Accurate identification of carbapenemases is essential to facilitate effective antibiotic treatment and reduce transmission of K. pneumoniae. This study aimed to detect carbapenemase production in carbapenem-resistant K. pneumoniae strains using phenotypic and genotypic methods. A total of 67 carbapenem-resistant K. pneumoniae strains obtained from various clinical samples were utilized for identification and antimicrobial susceptibility by the Vitek 2 Compact system (Biomerieux, France). Carbapenemase production was determined by using the Polymerase chain reaction, Blue-carba test (BCT) and Carbapenem inactivation method (CIM). Out of the isolates, 59 (88.1%) were positive bla OXA-48, 16 (23.9%) bla IMP, and five (7.5%) were positive bla NDM. No bla KPC genes were detected. The CIM identified 62 (92.5%), BCT identified 63 (94%) of PCR-positive isolates. The sensitivity and specificity of the BCT and the CIM were determined to be 96.7%, 40%, and 96.7%, 25% respectively. The bla OXA-48 gene was found to be the most prevalent in K. pneumoniae isolates. Early identification of carbapenem resistance plays a vital role in designing effective infection control strategies and mitigating the emergence and transmission of carbapenem resistance, thus reducing healthcare-associated infections.
Topics: Klebsiella pneumoniae; Humans; Phenotype; Microbial Sensitivity Tests; Genotype; Anti-Bacterial Agents; Carbapenems; beta-Lactamases; Polymerase Chain Reaction; Bacterial Proteins; Klebsiella Infections; Carbapenem-Resistant Enterobacteriaceae
PubMed: 38922280
DOI: 10.1590/0001-3765202420231322 -
Nanomaterials (Basel, Switzerland) Jun 2024A new curcuminoid molecule () has been designed and synthesized, containing a central -(CH)-COOH chain at the α carbon of the keto-enol moiety in the structure. The...
A new curcuminoid molecule () has been designed and synthesized, containing a central -(CH)-COOH chain at the α carbon of the keto-enol moiety in the structure. The carboxylic acid group is added to react with exposed amino groups on silica oxide nanoparticles (nSiO), forming an amide bond to attach the curcuminoid moiety to the nSiO covalently. The Kaiser test quantifies the functionalization degree, yielding 222 μmol of curcuminoid per gram of nanoparticles. The synthesized hybrid nanosystem, nSiO-NHCO-CCM, displays significant emission properties, with a maximum emission at 538 nm in dichloromethane, similar to curcuminoid (without the central chain), which emits at 565 nm in the same solvent. Solvent-induced spectral effects on the absorption and emission bands of the new hybrid nanosystem are confirmed, similar to those observed for the free curcuminoid (). The new nanosystem is evaluated in the presence of kerosene in water, showing an emission band at 525 nm as a detection response. The ability of nSiO-NHCO-CCM to change its fluorescence when interacting with kerosene in water is notable, as it overcomes the limitation caused by the insolubility of free curcuminoid in water, allowing for the exploitation of its properties when connected to the water-stable nanosystem for future detection studies.
PubMed: 38921898
DOI: 10.3390/nano14121022 -
Marine Drugs Jun 2024The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is , a type of green...
Green Seaweed as a Novel Non-Small Cell Lung Cancer Inhibitor in Overcoming Tyrosine Kinase Inhibitor Resistance: An Analysis Employing Network Pharmacology, Molecular Docking, and In Vitro Research.
The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is , a type of green algae known as green seaweed, seagrapes, or green caviar. This organism stands out because it has great promise for use in medicine, especially in the study of cancer. Through the utilization of computational modeling (in silico) and cellular laboratory experiments (in vitro), the chemical components included in the green seaweed were effectively analyzed, uncovering its capability to treat non-small cell lung cancer (NSCLC). The study specifically emphasized blocking SRC, STAT3, PIK3CA, MAPK1, EGFR, and JAK1 using molecular docking and in vitro. These proteins play a crucial role in the EGFR Tyrosine Kinase Inhibitor Resistance pathway in NSCLC. The chemical Caulersin (C2) included in extract (CRE) has been identified as a potent and effective agent in fighting against non-small cell lung cancer (NSCLC), both in silico and in vitro. CRE and C2 showed a level of inhibition similar to that of osimertinib (positive control/NSCLC drug).
Topics: Humans; Molecular Docking Simulation; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Protein Kinase Inhibitors; Caulerpa; Drug Resistance, Neoplasm; Network Pharmacology; Cell Line, Tumor; Seaweed; Antineoplastic Agents; Plant Extracts; ErbB Receptors; Acrylamides; Tyrosine Kinase Inhibitors
PubMed: 38921583
DOI: 10.3390/md22060272 -
Marine Drugs May 2024Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence...
Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.
Topics: Humans; Sulfonamides; Leukemia, Myeloid, Acute; Histone Deacetylase Inhibitors; Drug Synergism; Bridged Bicyclo Compounds, Heterocyclic; Apoptosis; Cell Line, Tumor; Antineoplastic Agents; Histone Deacetylase 1; Histone Deacetylases; Animals; Caspase 3; Myeloid Cell Leukemia Sequence 1 Protein
PubMed: 38921561
DOI: 10.3390/md22060250 -
Gels (Basel, Switzerland) Jun 2024To realize the effective profile control of a heavy oil reservoir, hydrolyzed polyacrylamide (HPAM) and water-soluble phenol-formaldehyde resin (PR) were chosen to...
To realize the effective profile control of a heavy oil reservoir, hydrolyzed polyacrylamide (HPAM) and water-soluble phenol-formaldehyde resin (PR) were chosen to prepare the profile control system, which gelled at medium or low temperatures and existed stably at high temperatures in the meantime. The effects of phenolic ratios, PR concentration, and HPAM concentration on the formation and strength of the gels were systematically studied by the gel-strength code method and rheological measurements. And the microstructure of the gels was investigated by scanning electron microscope measurements. The results showed that the gelling time of the HPAM-PR system was 13 h at 70 °C. The formed gel could stay stable for 90 days at 140 °C. In addition, the gels showed viscoelastic properties, and the viscosity reached 18,000 mPa·s under a 1.5 s shearing rate due to their three-dimensional cellular network structure. The formation of the gels was attributable to the hydroxyl groups of the PR crosslinking agent, which could undergo the dehydration condensation reaction with amide groups under non-acidic conditions and form intermolecular crosslinking with HPAM molecules. And the organic crosslinker gel system could maintain stability at higher temperatures because covalent bonds formed between molecules.
PubMed: 38920959
DOI: 10.3390/gels10060413 -
Cells Jun 2024Venetoclax and obinutuzumab are becoming frontline therapies for chronic lymphocytic leukemia (CLL) patients. Unfortunately, drug resistance still occurs, and the...
Lysosome-Disrupting Agents in Combination with Venetoclax Increase Apoptotic Response in Primary Chronic Lymphocytic Leukemia (CLL) Cells Mediated by Lysosomal Cathepsin D Release and Inhibition of Autophagy.
Venetoclax and obinutuzumab are becoming frontline therapies for chronic lymphocytic leukemia (CLL) patients. Unfortunately, drug resistance still occurs, and the combination could be immunosuppressive. Lysosomes have previously been identified as a target for obinutuzumab cytotoxicity in CLL cells, but the mechanism remains unclear. In addition, studies have shown that lysosomotropic agents can cause synergistic cell death in vitro when combined with the BTK inhibitor, ibrutinib, in primary CLL cells. This indicates that targeting lysosomes could be a treatment strategy for CLL. In this study, we have shown that obinutuzumab induces lysosome membrane permeabilization (LMP) and cathepsin D release in CLL cells. Inhibition of cathepsins reduced obinutuzumab-induced cell death in CLL cells. We further determined that the lysosomotropic agent siramesine in combination with venetoclax increased cell death in primary CLL cells through an increase in reactive oxygen species (ROS) and cathepsin release. Siramesine treatment also induced synergistic cytotoxicity when combined with venetoclax. Microenvironmental factors IL4 and CD40L or incubation with HS-5 stromal cells failed to significantly protect CLL cells from siramesine- and venetoclax-induced apoptosis. We also found that siramesine treatment inhibited autophagy through reduced autolysosomes. Finally, the autophagy inhibitor chloroquine failed to further increase siramesine-induced cell death. Taken together, lysosome-targeting drugs could be an effective strategy in combination with venetoclax to overcome drug resistance in CLL.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Lysosomes; Apoptosis; Autophagy; Cathepsin D; Reactive Oxygen Species; Drug Synergism; Cell Line, Tumor
PubMed: 38920669
DOI: 10.3390/cells13121041 -
Cells Jun 2024Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals...
Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV's imprint on cell metabolism.
Topics: Proline; Humans; Hepacivirus; Polyamines; Urea; Virus Replication; Arginase; Antiviral Agents; Hepatitis C; Cell Line, Tumor; Proline Oxidase
PubMed: 38920664
DOI: 10.3390/cells13121036 -
The Journal of Physical Chemistry. C,... Jun 2024[This corrects the article DOI: 10.1021/acs.jpcc.4c01994.].
[This corrects the article DOI: 10.1021/acs.jpcc.4c01994.].
PubMed: 38919727
DOI: 10.1021/acs.jpcc.4c03368