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PubMed2026

Quality-of-life assessment in the randomized JBCRG-M06/EMERALD study of eribulin plus dual HER2 blockade in HER2-positive locally advanced or metastatic breast cancer.

BACKGROUND: Although taxanes are a mainstay treatment for locally advanced or metastatic breast cancer (LABC/MBC), they often impair quality of life (QoL). Treatments that avoid taxane-related QoL deteriorations would be valuable. METHODS: The JBCRG-M06/EMERALD trial (NCT03264547, UMIN000027938) compared eribulin with a taxane, each combined with trastuzumab and pertuzumab, in patients with human epidermal growth factor receptor type 2 (HER2)-positive LABC/MBC. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module C30 (EORTC QLQ-C30) version 3.0. QoL deterioration was defined as a decrease in the Global Health Status (GHS) score by ≥ 10 points (minimum clinically important difference), disease progression, or death. RESULTS: QoL data were available for 210 (of 224 randomized) and 205 (of 222 randomized) patients in the eribulin and taxane groups, respectively. The median (95% confidence interval) time to QoL deterioration was 7.16 (6.28-8.34) months in the eribulin group versus 4.57 (4.17-6.14) months in the taxane group, with a hazard ratio of 0.80 (95% confidence interval 0.65-0.98; log-rank P = 0.08). QoL was maintained at 6 and 12 months in greater proportions of the eribulin group (62.7% and 30.5%) compared with the taxane group (43.5% and 25.5%). GHS scores remained stable over time in the eribulin group. GHS deteriorated between weeks 9 and 27 in the taxane group (i.e. during treatment) with subsequent recovery toward baseline. CONCLUSIONS: Eribulin could help avoid the early deteriorations in QoL that occur during taxane therapy and maintain QoL for longer in patents with HER2-positive LABC/MBC receiving trastuzumab and pertuzumab.

Adult↗
PubMed1979

The presence of a Ca2+ bridge within the gamma chain of human fibrinogen.

The presence of Ca2+ increased the mobility of fragment D, and the gamma chain from fibrinogen on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate, suggesting that a Ca2+ was associated with these fibrinogen derivatives. The mobilities of the constituent chains from fragment D produced under various conditions, indicate that Ca2+ bound to fibrinogen form an intrachain bridge towards the C-terminus of each gamma chain.

Binding Sites↗
PubMed1977

Localization of the membrane perturber adamantylsulfate in sarcoplasmic reticular vesicles.

The properties of a new membrane perturbing agent, adamantyl sulfate (A-1-S) are described. Lobster sarcoplasmic reticular vesicles (SRV) were used as a test membrane system and the activity of the Ca2+--Mg2+-dependent ATPase in conjunction with spin label data was used to determine the location of A-1-S in the membrane. The results suggest that A-1-S perturbs only the polar region of the SRV and that this causes loss of ATPase function. Thus, ATPase activity requires integrity of the membrane polar region.

Adamantane↗
PubMed2026

Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.

BACKGROUND: The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. PATIENTS AND METHODS: Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). RESULTS: Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. CONCLUSION: Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.

Aged↗
PubMed1975

Tetramethylenedisulphotetramine: an inhibitor of gamma-aminobutyric acid induced depolarization of the isolated superior cervical ganglion of the rat.

Tetramethylenedisulphotetramine (TETS), a potent convulsant, antagonized the depolarizing action gamma-aminobutyric acid (GABA) in the isolated superior cervical ganglion of the rat. No antagonism of responses to the cholinomimetic agent carbachol was observed. TETS appeared to act in a non-competitive manner and was reversible. Its activity profile was comparable to that of bicuculline in the same tissue except that the latter appears to act in a competitive manner.

Aminobutyrates↗
PubMed1977

Effects of small-particle aerosols of rimantadine and ribavirin on arterial blood pH and gas tensions and lung water content of A2 influenza-infected mice.

The respiratory pathophysiology of A2 influenza infection was studied in mice treated with small-particle aerosols (SPA) of rimantadine or ribavirin. Untreated infections in mice resulted in survival rates of 15% or less and were characterized by (i) severe hypoventilation (decreased P(O2) and increased P(CO2)), (ii) compensated respiratory acidosis (increased P(CO2) and HCO(3) (-), with normal pH), (iii) pneumonia with increased ratio of wet/dry lung weight, and (iv) hypothermia. Treatment with SPA of rimantadine (21 mg/kg per day for 4 days) beginning 72 h after virus challenge significantly improved survival rate (80%) but failed to alter lung pathology from that found in infected, untreated mice. Rimantadine treatment decreased somewhat the severity of hypoventilation, respiratory acidosis, lung wet weight, hypothermia, and lung virus titers from that observed in infected, untreated mice. SPA of ribavirin (26 mg/kg per day for 4 days) initiated 6 h after SPA exposure of mice to virus significantly improved survival rate (95%) and reduced lung virus titers and lung pathology. Gas exchange and pulmonary edema in ribavirin-treated, infected mice were significantly improved over those of infected, untreated controls. The mechanisms for increased survival rates induced by SPA of rimantadine remain uncertain, since increased survival rates could not be ascribed entirely to improvements in lung functions. In contrast, however, ribavirin treatment appeared to improve survival rates by reducing major lung pathology and pulmonary dysfunction. This was probably mediated through the antiviral effects of ribavirin.

Adamantane↗
PubMed1975

[The effect of 1-adamantyl radicals on curare-like activity].

In the series of polymethylene bis-ammonium salts R(CH3)2N(CH2)NN(CH3)2R . 2I--(R=CH3 or Ad) a study was made of the significance of hydrophobic 1-adamantyle radicals (1--Ad) for curare-like activity. Administration of 1-ad radicals into the cation groups of depolarizing agents (n-9--11) altered their mechanism of action and diminished their activity. Attachmeni of 1-Ad radicals to the both quarternary nitrogen atoms of the antidepolarizing agents (n=5 and 6) sharply increased their curare-like activity. The data obtained pointed to the presence of hydrophobic zones in the cholinoreceptors of skeletal muscles.

Adamantane↗
PubMed1978

[Effect of cross-linking agents on mechanical properties of a fluid resin (author's transl)].

Effect of several cross-linking agents added to MMA on the mechanical properties of self-cured fluid resins was studied. The cross-linking agents were 2,2-bis (4-methacryloxyethoxyphenyl) propane, trimethylolpropane trimethacrylate, neopentylglycol dimethacrylate, hexamethyleneglycol dimethacrylate and 1,2-polybutadiene. Their concentrations in MMA were 1,3,5 and 10 wt%. Measured mechanical properties were Brinell hardness, tensile strength, impact strength and transverse strength. The best composition was 5% neopentylglycol dimethacrylate in MMA among studied samples. Microscopic observation of the surface after tensile test suggested that diffusibility of cross-linking agents into PMMA powder affected the mechanical properties. Mechanical properties of both matrix and powder, and their adhesion at the interface had influence upon the mechanical properties of resins processed by powder-liquid method.

Acrylates↗
PubMedDate not supplied

[Study of the effect of rimantadine on the course of mixed viral-bacterial infection in albino mice].

The results of the study of rimantadine effectiveness in a viral-bacterial infection in white mice caused by a mixture of influenza A2 virus (10 LD50) and hemolytic streptococcus group A (350 million bacteria). The drug showed no prophylactic or therapeutic effect in the mixed infection, whereas in influenza infection in the animals which served as a positive control rimantadine had marked antiviral activity (P less than 0.001). It is assumed that the lack of the drug effectiveness against the mixed infection is due to the formation in the animals of virus-microbe complexes which are conducive to an increase of infectious virus titers and virus resistance to various treatments.

Adamantane↗
PubMedDate not supplied

Metabolic reduction of 1-nitrosoadamantane by rabbit liver microsomes. Properties of a C-nitroso reductase system.

Washed microsomes from rabbit liver reduced 1-nitrosoadamantane to N-hydroxy-1-aminoadamantane in the presence of a cofactor solution under aerobic conditions; no further reduction of the hydroxylamino metabolite to 1-aminoadamantane (amantadine) occurred. Reduced pyridine nucleotide cofactors are needed for the metabolic reduction. The rate of formation of N-hydroxy-1-aminoadamantane depended upon the microsomal protein content, the time of incubation and the concentration of 1-nitrosoadamantane incubated. The metabolic reduction occurred in air as well as under nitrogen or carbon monoxide. Cupric chloride, mercuric chloride, cysteamine, FAD, and FMN decreased significantly the C-nitroso reductase. The properties of the C-nitroso reductase differed from those of other microsomal reductive pathways.

Adamantane↗