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Afatinib Versus Osimertinib for Non-Small Cell Lung Cancer With Uncommon EGFR Mutations: Real-World Outcomes.

Non-small cell lung cancers (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations (UMs) are clinically heterogeneous, and the optimal first-line EGFR tyrosine kinase inhibitor (EGFR-TKI), as well as the role of subsequent immune checkpoint inhibitor (ICI)-based regimens, remains uncertain. We conducted a multicenter retrospective cohort study including patients with advanced or recurrent non-squamous NSCLC harboring UMs who received first-line afatinib or osimertinib between January 2015 and January 2024 at 29 hospitals in Japan, excluding exon 20 insertions and de novo

Esophageal cancer as initial presentation of Fanconi anemia in patients with a hypomorphic FANCA variant.

Fanconi anemia (FA) is a clinically heterogenous and genetically diverse disease with 22 known complementation groups (FA-A to FA-W), resulting from the inability to repair DNA interstrand cross-links. This rare disorder is characterized by congenital defects, bone marrow failure, and cancer predisposition. FANCA is the most commonly mutated gene in FA and a variety of mostly private mutations have been documented, including small and large indels and point and splicing variants. Genotype-phenotype associations in FA are complex, and a relationship between particular FANCA variants and the obs

Cisplatin-induced ototoxicity: the effect of pigmentation and inhibitory agents.

Cis-diamminedichloroplatinum II (cisplatin), a divalent platinum compound and potent cell-cycle nonspecific chemotherapeutic agent, produces a dose-limiting, permanent, high-frequency sensori-neural hearing loss and peripheral neuropathy, and a dose-related cumulative renal insufficiency with tubular necrosis and interstitial nephritis. The potential for dose-limiting and permanent cochlear (neuro) toxicity remains despite present methods of hypertonic saline, prehydration, and mannitol diuresis prior to drug administration. The exact mechanism(s) of ototoxicity and/or nephrotoxicity are still

Monobenzyltin Complex C1 Induces Apoptosis in MCF-7 Breast Cancer Cells through the Intrinsic Signaling Pathway and through the Targeting of MCF-7-Derived Breast Cancer Stem Cells via the Wnt/β-Catenin Signaling Pathway.

Monobenzyltin Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, C1, is an organotin non-platinum metal-based agent. The present study was conducted to investigate its effects on MCF-7 cells with respect to the induction of apoptosis and its inhibitory effect against MCF-7 breast cancer stem cells. As determined in a previous study, compound C1 revealed strong antiproliferative activity on MCF-7 cells with an IC50 value of 2.5 μg/mL. Annexin V/propidium iodide staining coupled with flow cytometry indicated the induction of a

Auranofin Potentiates Cisplatin Response in the Setting of Context-Dependent NOTCH-Associated Signaling States in Endometrial Cancer.

UNLABELLED: Therapeutic resistance remains a major challenge in advanced and recurrent endometrial cancer. Aberrant NOTCH signaling has been associated with aggressive tumor behavior and therapeutic resistance across multiple malignancies, yet its therapeutic significance in endometrial cancer remains incompletely defined. We investigated whether auranofin (AuR), a pleiotropic gold-containing compound that inhibits thioredoxin reductase and can disrupt RBPJ chromatin occupancy, alters platinum responsiveness in endometrial cancer models. Upper-quartile NOTCH3 copy number was associated with po

Therapeutic dosing and targeting efficacy of Pt-Mal-LHRH towards triple negative breast cancer.

OBJECTIVE: Pt-Mal-LHRH is a newly synthesized chemotherapeutic agent that was designed to selectively target the luteinizing hormone-releasing hormone (LHRH) receptor expressed by triple negative breast cancer (TNBC). The aim of this study was to evaluate the therapeutic dosing, tumor reduction efficacy, and selective distribution of Pt-Mal-LHRH in-vivo. METHODS AND RESULTS: LHRH tissue expression levels in-vivo were investigated using western blotting and LHRH was found to be increased in reproductive tissues (mammary, ovary, uterus). Further, Pt-Mal-LHRH was found to have increased TNBC tum

Heterobinuclear copper(II)‑platinum(II) complexes with oxindolimine ligands: Interactions with DNA, and inhibition of kinase and alkaline phosphatase proteins.

Two mononuclear copper(II) compounds, [Cu(isad)(H2O)Cl]Cl 1 and [Cu(isah)(H2O)Cl]Cl 2, and its corresponding heterobinuclear species containing also platinum(II), [CuCl(isad)Pt(NH3)Cl2] 3 and [CuCl(isah)Pt(NH3)Cl2] 4 (where isad and isah are oxindolimine ligands, (E)-3-(2-(3-aminopropylamino)ethylimino)indolin-2-one, and (E)-3-(3-amino-2-hydroxypropylimino)indolin-2-one, respectively), have been previously synthesized and characterized by different spectroscopic techniques in our laboratory. Cytotoxicity assays performed with B16F10 murine cancer cells, and MES-SA human uterine sarcoma cells,

Oxaliplatin: a review of its use in the management of metastatic colorectal cancer.

UNLABELLED: Oxaliplatin is a cytotoxic agent which, like other platinum compounds, acts primarily by causing inter- and intra-strand cross-links in DNA, thereby inhibiting DNA synthesis. Oxaliplatin has a bulky carrier ligand which is thought to enhance cytotoxicity and abolish cross-resistance between oxaliplatin and other platinum compounds. Phase II and III clinical trials have found oxaliplatin combined with fluorouracil/calcium folinate (leucovorin/folinic acid) to be an effective first- and second-line treatment for patients with metastatic colorectal cancer. First-line triple therapy wi…

Synthesis of PtRu5(CO)14(PBu(t)3)(mu-H)2(mu6-C) and its reactions with Pt(PBut3)2, HGePh3, and HSnPh3.

Reaction of PtRu5(CO)15(PBut3)(C), 3, with hydrogen at 97 degrees C yielded the new dihydride-containing cluster compound PtRu5(CO)14(PBut3)(mu-H)2(mu6-C), 5. Compound 5 was characterized crystallographically and was shown to contain an octahedral cluster consisting of one platinum and five ruthenium atoms with a carbido ligand in the center. Two hydrido ligands bridge two oppositely positioned PtRu bonds. Compound 5 reacts with Pt(PBut3)2 to yield Pt2Ru5(CO)14(PBut3)2(mu-H)2(mu6-C), 6, a Pt(PBut3) adduct of 5, by adding a Pt(PBut3) group as a bridge across one of the Ru-Ru bonds in the square

What is the Reason That the Pharmacological Future of Chemotherapeutics in the Treatment of Lung Cancer Could Be Most Closely Related to Nanostructures? Platinum Drugs in Therapy of Non-Small and Small Cell Lung Cancer and Their Unexpected, Possible Interactions. The Review.

Over the course of several decades, anticancer treatment with chemotherapy drugs for lung cancer has not changed significantly. Unfortunately, this treatment prolongs the patient's life only by a few months, causing many side effects in the human body. It has also been proven that drugs such as Cisplatin, Carboplatin, Oxaliplatin and others can react with other substances containing an aromatic ring in which the nitrogen atom has a free electron group in its structure. Thus, such structures may have a competitive effect on the nucleobases of DNA. Therefore, scientists are looking not only for

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… Platinum Compounds Platinum compounds are among the first, most effective, and most frequently used chemotherapy drugs. … Their main reason is the poor selectivity of Platinum compounds. …

Metallodrugs are unique: opportunities and challenges of discovery and development.

Metals play vital roles in nutrients and medicines and provide chemical functionalities that are not accessible to purely organic compounds. At least 10 metals are essential for human life and about 46 other non-essential metals (including radionuclides) are also used in drug therapies and diagnostic agents. These include platinum drugs (in 50% of cancer chemotherapies), lithium (bipolar disorders), silver (antimicrobials), and bismuth (broad-spectrum antibiotics). While the quest for novel and better drugs is now as urgent as ever, drug discovery and development pipelines established for orga

P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-fluorouracil: implication in resistance.

5-Fluorouracil (5-FU), together with other drugs such as oxaliplatin, is one of the most important pharmacological agents in the treatment of colorectal cancer. Although mitogen-activated protein kinases (MAPKs) have been extensively connected with resistance to platinum compounds, no role has been established in 5-FU resistance. Here we demonstrate that p38MAPK activation is a key determinant in the cellular response to 5-FU. Thus, inhibition of p38MAPKα by SB203580 compound or by short-hairpin RNA interference-specific knockdown correlates with a decrease in the 5-FU-associated apoptosis and…

Contact hypersensitivity to disodium hexachloroplatinate in mice.

Complex platinum (Pt) compounds are known as occupational respiratory sensitizers whereas their role in skin exposure is unclear. In this study, both skin irritation and induction of contact hypersensitivity by halide Pt salts were characterized in mice. Repeated application of Na2[PtCl6] (5% in acetone) to both ears of naive BALB/c mice induced activation of the draining auricular lymph nodes. Flow cytometric analysis revealed a striking increase in the number of lymph node cells expressing proliferating cell nuclear antigen. In separate experiments, Na2[PtCl6] or acetone were applied only to

Photoactivated triple-signal amplification in engineered Pt-Fc-MOFs for rapid and visual detection of foodborne antibiotics.

The rational design of a photoactivated platinum–ferrocene-based metal–organic framework (Pt-Fc-MOF) biosensing platform is reported featuring triple-signal amplification for the rapid and visual detection of chloramphenicol (CAP) residues. The system combines aptamer-coated magnetic nanoparticles, cDNA-linked Pt-Fc-MOFs, and light-enhanced catalysis for triple-signal amplification. Upon specific target recognition, CAP binding induces aptamer conformational change, triggering the release of signal probes via nucleic acid strand displacement. The liberated Pt-Fc-MOFs incorporate ferrocene and

Real World Patient Eligibility for Second Line Lurbinectedin Based Treatment in Small Cell Lung Cancer: Understanding Epidemiology and Estimating Health Care Utilization.

BACKGROUND: In the ATLANTIS study, second-line lurbinectedin/doxorubicin did not improve overall survival (OS), however patients with a chemotherapy-free interval (CTFI) of ≥180 days had an improved progression free survival (PFS). The objective of this retrospective study was to identify the proportion of real-world small cell lung cancer (SCLC) patients who are suitable for lurbinectedin-based therapy based on these criteria. METHODS: A retrospective study of all SCLC referred to BC Cancer between 2012 and 2017 was conducted. Patient demographics, staging, treatment, and survival data were

PEG-PtS2 nanosheet-based fluorescence biosensor for label-free human papillomavirus genotyping.

A simple and efficient ultrasonication-assisted liquid exfoliation method is proposed to produce PtS2 nanosheets on a large scale and improve their dispersion in aqueous solution by surface polyethylene glycol modification. The interaction of polyethylene glycol-modified PtS2 (PEG-PtS2) nanosheets with fluorescent labeled DNA and the fluorescence quenching mechanism using FAM-labeled hpv16e6 gene fragment as a probe was investigated. The excitation and emission wavelengths were 468 and 517 nm, respectively. The fluorescence quenching mechanism of PEG-PtS2 nanosheets for double-stranded DNA (ds

Patterns of relapse after chemotherapy in patients with high-risk non-seminomatous germ cell tumor.

OBJECTIVES: We investigated the pattern of relapse after chemotherapy in patients with high-risk germ cell tumor (GCT) to critically review common follow-up procedures including close monitoring of serum tumor markers and radiologic procedures. METHODS: 645 patients received first-line (434 patients) or salvage platinum-based (211 patients) high-dose chemotherapy in three multicenter trials. Retrospective analysis comprised 77 patients after first-line and 61 after salvage chemotherapy, who had achieved at least a partial remission but progressed afterwards. RESULTS: At relapse, 24% of the p

Room temperature hydrogen detection using 1-D nanostructured tin oxide sensor.

Room temperature sensing of hydrogen using randomly oriented tin oxide nanowires has been demonstrated successfully. The role of surface functionalization of nanowires with platinum catalyst in rapid hydrogen detection is also studied. These nanowires were successfully incorporated into a micro-electro-mechanical (MEMS) device. The device can successfully detect hydrogen gas (as low as 500 ppm) with response time as low as 10 sec. Effect of aspect ratio of the nanowires on diffusion of hydrogen molecules in the tin oxide nanowires is elucidated in detail.

Melphalan for the treatment of patients with recurrent epithelial ovarian cancer.

The purpose of this study was to determine the response to melphalan in patients with recurrent epithelial ovarian cancer after platinum-based therapy. This retrospective observational study analyzed 10 patients with recurrent epithelial ovarian carcinoma treated with melphalan between August 1995 and April 2001. All had received primary platinum-based therapy. Nine of the 10 patients had chemosensitive disease. All but one patient had received one or more second-line therapies prior to melphalan. The median time to recurrence after first-line therapy was 26 months (range, 3-68). Treatment wit

Liposomes as drug carrier system for cis-diamminedichloroplatinum (II). II. Antitumor activity in vivo, induction of drug resistance, nephrotoxicity and Pt distribution.

In this study we have investigated the use of liposomes as a drug carrier system for cis-diamminedichloroplatinum(II) (cis-DDP) in order to reduce the nephrotoxicity with preservation of antitumor activity. Liposomes (PC/PS/Chol 10:1:4) were prepared using hydration media containing no or a relatively low concentration of NaCl. It was found that cis-DDP containing liposomes (lip cis-DDP) injected i.v. to IgM immunocytoma-bearing LOU/M rats at a dose of 1 mg cis-DDP/kg (cumulative dose 7 mg cis-DDP/kg) showed less antitumor activity than the free drug. The optimal cumulative dose of free cis-DD