Imaging rotational energy transfer: comparative stereodynamics in CO + N2 and CO + CO inelastic scattering.

State-to-state rotational energy transfer in collisions of ground ro-vibrational state 13CO molecules with N2 molecules has been studied using the crossed molecular beam method under kinematically equivalent conditions used for 13CO + CO rotationally inelastic scattering described in a previously published report (Sun et al., Science, 2020, 369, 307-309). The collisionally excited 13CO molecule products are detected by the same (1 + 1' + 1'') VUV (Vacuum Ultra-Violet) resonance enhanced multiphoton ionization scheme coupled with velocity map ion imaging. We present differential cross sections and scattering angle resolved rotational angular momentum alignment moments extracted from experimentally measured 13CO + N2 scattering images and compare them with theoretical predictions from quasi-classical trajectories (QCT) on a newly calculated 13CO-N2 potential energy surface (PES). Good agreement between experiment and theory is found, which confirms the accuracy of the 13CO-N2 potential energy surface for the 1460 cm-1 collision energy studied by experiment. Experimental results for 13CO + N2 are compared with those for 13CO + CO collisions. The angle-resolved product rotational angular momentum alignment moments for the two scattering systems are very similar, which indicates that the collision induced alignment dynamics observed for both systems are dominated by a hard-shell nature. However, compared to the 13CO + CO measurements, the primary rainbow maximum in the DCSs for 13CO + N2 is peaked consistently at more backward scattering angles and the secondary maximum becomes much less obvious, implying that the 13CO-N2 PES is less anisotropic. In addition, a forward scattering component with high rotational excitation seen for 13CO + CO does not appear for 13CO-N2 in the experiment and is not predicted by QCT theory. Some of these differences in collision dynamics behaviour can be predicted by a comparison between the properties of the PESs for the two systems. More specific behaviour is also predicted from analysis of the dependence on the relative collision geometry of 13CO + N2 trajectories compared to 13CO + CO trajectories, which shows the special 'do-si-do' pathway invoked for 13CO + CO is not effective for 13CO + N2 collisions.

Detection of the O2 A'3ΔU Herzberg III state by photofragment imaging.

Photofragment imaging is shown to provide a sensitive method for detection of the O2 A'3Δu Herzberg III state using a one-laser dissociation/O(1D) resonance enhanced multiphoton ionization (REMPI) scheme with a focused nanosecond dye laser beam tuned to 203.8 or 205.2 nm, combined with velocity map imaging of the atomic oxygen photofragment. O2 populated in the Herzberg states is generated by photodesorption at 250 nm of solid O2 ice held at 15 K and by an electric discharge in a pulsed molecular beam of pure O2. Ice photo-desorption results in Herzberg state products with higher translational, vibrational and rotational energy spreads, yielding the same signal as the discharge source but with lower velocity resolution. A clear signal with parallel character (ß âˆ¼ 0.9) assigned to dissociation of O2 A'3Δu(v = 0, 1 Ω = 1) was observed when using a pulsed electric discharge source under specific 'cold' conditions with O(1D) detection, driving one-photon dissociation around 205 nm. No products corresponding to O2 A'3Δu state dissociation were observed for 225.625 or 200.32 nm dissociation with O(3P2) detection, which implies that the O2 A'3Δu state dissociates exclusively to the third (O1D + O1D) dissociation limit. Dissociation is suggested to take place through the 21Πg upper state to the O1D + O1D limit where spin-orbit coupling of the A'3Δu state with the 11Πu state accesses the allowed parallel 1Πu → 1Πg transition. While the absence of a parallel-type photodissociation signal from the c1Σ-u state may be expected, the A3Σ+u should spin-orbit couple through the same pathway as the A'3Δu state. The fact that no clear A3Σ+u signal is observed suggests a faster deactivation process compared to the A'3Δu state in the discharge and ice desorption process.

An updated review on the efficacy of adjuvant endocrine therapies in hormone receptor-positive early breast cancer.

The third-generation aromatase inhibitors (AIS) are largely replacing tamoxifen in the adjuvant treatment of early-stage breast cancer in postmenopausal women with hormone receptor-positive tumours. To date, multiple trials have been conducted comparing tamoxifen treatment with an AI, and all have demonstrated improved disease-free survival with AI treatment. Trials have included direct 5-year comparisons between tamoxifen and an AI, switching to an AI within 5 years after initial tamoxifen treatment, or extending treatment with an AI after 5 years of completed tamoxifen treatment. Some of these trials have been completed; others are ongoing; and head-to-head trial comparisons of individual AIS are also in progress. The present article summarizes the data obtained from various clinical trials of hormonal therapy for early breast cancer. It also reviews recent data so as to shed light on the current status of these therapies. The focus is on the efficacy of treatment with an AI. Toxicity is discussed in the second article in this supplement.

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Hormone replacement therapy in women with breast cancer. Do the risks outweigh the benefits?

PURPOSE: To review critically the literature regarding effects of estrogen replacement therapy (ERT)/combined estrogen and progesterone replacement therapy (HRT) on the risk of breast cancer and on other health risks and benefits in postmenopausal women, with a focus on risks and benefits in women with a previous diagnosis of breast cancer. METHOD: A literature search was conducted using Medline, Cancerline, and the bibliographies of reports published as of March 1995. All five published meta-analyses that examined the risk of breast cancer in relation to ERT/HRT in otherwise healthy women were critically reviewed. All known reports of women with a history of breast cancer given ERT/HRT subsequent to diagnosis and additional reports regarding the benefits of ERT/HRT were also reviewed. RESULTS: None of the five meta-analyses demonstrated a significantly increased risk of developing breast cancer in ever users compared with never users of ERT/HRT. Current use may be associated with a small increased risk. This increased risk should be balanced by the expected benefits of ERT/HRT on quality of life, bone metabolism, and cardiovascular function. Preliminary information does not suggest a major detrimental effect of ERT/HRT in women with a previous diagnosis of breast cancer, but these reports include few women with limited follow-up data. There are no randomized trials in women with a previous diagnosis of breast cancer. CONCLUSION: In healthy postmenopausal women, the benefits associated with ERT/HRT outweigh the risks. In women with a previous diagnosis of breast cancer, the balance of risks and benefits should be explored in randomized controlled trials.

An ongoing European organization for research and treatment of cancer crossover trial comparing single-agent paclitaxel and doxorubicin as first- and second-line treatment of advanced breast cancer.

The activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in advanced breast cancer patients who have failed doxorubicin treatment is well established, but the optimal sequence between these two important agents remains to be determined. The European Organization for Research and Treatment of Cancer therefore designed a prospective randomized clinical trial in which patients not exposed to anthracyclines in the adjuvant setting received either first-line paclitaxel, given as a 3-hour infusion at a dose of 200 mg/m2 followed at the time of disease progression by second-line doxorubicin, given as a bolus injection at a dose of 75 mg/m2 or the reverse sequence. The target accrual is 330 patients. Interim results on 207 evaluable patients of 289 randomized are presented.

Tolerance to nicotine-induced sympathoadrenal stimulation and cross-tolerance to stress: differential central and peripheral mechanisms in rats.

Nicotine stimulates the secretion of catecholamines from sympathetic nerve endings and adrenal medulla by acting on peripheral nicotinic cholinergic receptors. Nicotine is also a potent stimulant in the central nervous system but the significance of nicotinic receptors in brain in mediating cardiovascular and sympathoadrenal responses to nicotine is unclear. The responses of resting plasma catecholamines, blood pressure and heart rate were compared in rats receiving nicotine, administered either systemically or intracerebroventricularly (i.c.v.). Sympathoadrenal stress responses were also studied in rats rendered tolerant to nicotine from repeated systemic or intraventricular injections. Nicotine, given either intraventricularly or systemically, produced dose-related increases in the concentration of epinephrine in plasma. Little effect on norepinephrine in plasma was observed with nicotine given intraventricularly, indicating predominant stimulation of adrenomedullary pathways. In contrast, nicotine, given systemically, produced comparable increases in both epinephrine and norepinephrine. Blood pressure increased and heart rate fell in response to either intraventricular or systemic administration of nicotine. Rats exhibited tolerance to nicotine 24 hr after a single intraventricular injection; however, tolerance was not detected with systemically injected nicotine unless the injections were given at least every 30 min. Whereas rats rendered tolerant to systemic administration of nicotine were cross-tolerant to stress, with respect to sympathoadrenal stimulation, cross-tolerance with stress was not detected in rats treated with nicotine repeatedly by the intraventricular route. These results indicate that nicotinic receptors in brain modulate the central sympathetic outflow and adapt readily to nicotine stimulation with prolonged tolerance, but are probably not involved in sympathoadrenal stress responses. Peripheral nicotinic receptors, regulating sympathoadrenal secretion of catecholamines, displayed much shorter-lasting tolerance.

Breast cancer therapies in development. A review of their pharmacology and clinical potential.

Although the management of breast cancer has improved over the past few decades, it remains an important challenge for the clinician. Cytotoxic chemotherapy and hormonotherapy, when given in the adjuvant setting, have a definitive though modest impact on the outcome of early-stage breast cancer. In metastatic disease, these therapies help to provide substantial palliation of symptoms but have a limited impact on survival. The discovery of vinorelbine and the taxanes, paclitaxel and docetaxel, certainly represented the most encouraging clinical development of the 1980s in breast cancer therapy. Several other new cytotoxic agents have been recognised for their potential in the treatment of this disorder. Many of them are only in a very early phase of their clinical development and it remains to be proven that they will have a major role in daily practice in the near future.

Hypothalamic opioid peptide regulation of catecholamine secretion.

We compared the plasma catecholamine responses to intracisternal beta-endorphin with those to two mu receptor agonists. Morphine was less potent and [D-Ala2, MePhe4, Gly5-ol]enkephalin (DAGO) was more potent in stimulating catecholamine secretion. Since the hypothalamic paraventricular nucleus (PVN) contains a high level of opioid binding sites and is important for sympathoadrenal regulation, we examined the effects on catecholamine secretion of DAGO infusion into the PVN. DAGO infused into the PVN produced dose-related increases in plasma catecholamine concentrations, with an effective dose as low as 10pmol. This DAGO effect was blocked by the prior systemic administration of naloxone, and DAGO was ineffective when infused into frontoparietal cortex. Thus, endogenous opioid peptides appear to increase central sympathetic outflow and catecholamine secretion by stimulating mu receptors in the PVN.

Mu receptors at discrete hypothalamic and brainstem sites mediate opioid peptide-induced increases in central sympathetic outflow.

Synthetic human beta-endorphin, 7.25 nmol intracisternally, in conscious, freely moving, cannulated adult male rats increased plasma concentrations of the 3 catecholamines, epinephrine, norepinephrine and dopamine. Similarly administered equimolar morphine increased only plasma epinephrine concentration significantly. A 10-fold greater intracisternal dose of morphine significantly increased plasma concentrations of all 3 catecholamines. This effect was inhibited by prior intra-arterial naloxone administration. Intracisternal administration of the selective mu receptor agonist [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin (DAGO), 2.9 nmol, also increased plasma concentrations of the 3 catecholamines and, furthermore, these effects were significantly greater than those noted in response to equimolar beta-endorphin. The greater potency of DAGO than beta-endorphin to increase catecholamine secretion suggests that this opioid peptide-induced effect is mediated at mu receptors. Administration of DAGO, 0.1 nmol, directly into either the hypothalamic paraventricular nucleus (PVN) or brainstem nucleus of the solitary tract (NTS) significantly increased plasma concentrations of all 3 catecholamines when compared with either saline-infused controls or animals administered DAGO into other brain areas. These catecholamine-stimulating effects of DAGO administered into either PVN or NTS were prevented by prior intra-arterial naloxone administration. Heart rate, but not mean arterial blood pressure, increased in response to DAGO administration into the NTS while no significant cardiovascular changes were noted among the experimental groups in response to DAGO administered into the PVN. These data support a hypothesis that mu receptors at discrete and anatomically distant brain sites mediate opioid peptide-induced catecholamine secretion through activation of the central sympathetic outflow to the adrenal medulla and sympathetic nerve terminals.