Coleman-Weinberg Abrikosov-Nielsen-Olesen strings

We study properties of Abrikosov-Nielsen-Olesen (ANO) strings with the Coleman-Weinberg (CW) potential, which we call CW-ANO strings. While the scale-invariant scalar potential has a topologically trivial vacuum admitting no strings at the classical level, quantum correction allows topologically nontrivial vacua and stable string solutions. We find that the system of the CW potential exhibits significant difference from that of the conventional Abelian-Higgs model with the quadratic-quartic potential. While a single-winding string is qualitatively similar in both systems, and the static intervortex force between two strings at large distance is attractive/repulsive in the type-I/II regime for both, that between two CW-ANO strings exhibits a nontrivial structure. It develops an energy barrier between them at intermediate distance, implying that the string with winding number $n > 1$ can constitute a metastable bound state even in the type-II regime. We name such a superconductor type-$\overline{1.5}$. We also discuss implications to high-energy physics and cosmology.Comment: 40 pages, 19 figs; v2: minor revisio

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy

Renal cell carcinoma; Immune checkpoint inhibitor; MetastaticCarcinoma de células renales; Inhibidor del punto de control inmunitario; MetastásicoCarcinoma de cèl·lules renals; Inhibidor del punt de control immunitari; MetastàticThe first-in-class, small molecule HIF-2α inhibitor, belzutifan, has demonstrated promising antitumor activity in previously treated patients with clear cell renal cell carcinoma (RCC). HIF-2α also regulates VEGF expression and is involved in resistance to anti-VEGF therapy. This study describes the rationale and design for a randomized, phase III study evaluating efficacy and safety of belzutifan plus the tyrosine kinase inhibitor (TKI) lenvatinib versus the TKI cabozantinib in patients with advanced RCC progressing after anti-PD-1/PD-L1 therapy in the first- or second-line setting or as adjuvant therapy. Considering the unmet need for effective and tolerable treatment of advanced RCC following immune checkpoint inhibitors, belzutifan plus lenvatinib may have a positive benefit/risk profile

Effects of exposure to cigarette smoke on intestinal propulsion in rats.

The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.</p

Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan

Comparison of the current study with other sorafenib-interferon combination studies and with single-agent sorafenib studies [25]. (XLSX 12 kb

Resection of Hepatic Metastasis from Colorectal Cancer : Survival, Factors Influencing Prognosis, and Follow-up

The purpose of this retrospective study was to analyze the surgical results of hepatic resection in our patients with colorectal hepatic metastasis. During a 26-year period, 223 patients among 1,484 patients with colorectal cancer suffered liver metastasis. In 44 curatively resected patients, the one-, three- and five-year cumulative survival rates were 85.9%, 44.9% and 23.0%, respectively. The prognostic importance of seven factors was evaluated. Synchronous or metachronous resection, the type of liver resection, and histologic differentiation did not influence the prognosis, whereas the number and size of metastases, and lymph node involvement did significantly affect prognosis as single factors. The mean diameter of metastatic lesions in the liver was 2.5 cm in the synchronous group and 4.5 cm in the metachronous group, the difference being significant (p = 0.0005). The presence of tumors with large diameters in the metachronous group might mean our failure of early detection of the recurrence of hepatic metastases. It is necessary to make steady efforts such as introducing regular follow-up imaging of colorectal cancer. The median interval between the primary operation and liver metastasis resection was 15.7 months in the lymph node involvement group and 37.7 months in the no lymph node involvement group. In 19 patients among 21 metachronously resected patients, the hepatic resection was done within three years. In conclusion, it was considered that hepatectomy could be done safely, that detection of an earlier lesion could improve the surgical results, and that follow-up for liver metastasis should be done intensively between 12 and 36 months after colorectal cancer surgery

Prognostic Impact of Genetic Polymorphism in Mineralocorticoid Receptor and Comorbidity With Hypertension in Androgen-Deprivation Therapy

Mineralocorticoid receptor (MR) signaling which is closely associated with hypertension plays important roles in resistance to antiandrogen therapy in prostate cancer. However, its impact on the prognosis in androgen-deprivation therapy (ADT) has not been elucidated. Then, we investigated the impact of genetic variation in MR and comorbidity with hypertension on the prognosis in ADT. This study included 182 Japanese patients with prostate cancer treated with ADT, whose comorbidity status with hypertension were available. The associations of MR polymorphism (rs5522) and comorbidity with hypertension with clinicopathological parameters as well as progression-free survival and overall survival were examined. Clinicopathological characteristics were comparable between genetic variation in MR. However, homozygous variant in MR was associated with shorter time to castration resistance (P = 0.014) and any-cause death (P = 0.024). In patients' background, presence of comorbidity with hypertension showed the trend with lower PSA level at diagnosis and lower biopsy Gleason score, as well as significant association with less incidence of N1. Comorbidity with hypertension was associated with longer time to castration resistance (P = 0.043) and any-cause death (P = 0.046), which was diminished on multivariate analysis including age, PSA level at diagnosis, biopsy Gleason score, clinical stage, and the modality of hormonal therapy. Genetic variation in MR (rs5522) and comorbidity with hypertension were significantly and potentially associated with prognosis when treated with ADT, respectively. This suggests that the individual intensity of MR signaling may be associated with resistance to ADT and a promising biomarker in ADT

Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms

IntroductionThe phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.MethodsIn CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.ResultsIn all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.ConclusionEfficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.Clinical trial registrationClinicalTrials.gov, identifier NCT0281186