Genetic parameters for somatic cell score, milk yield and type traits in Nigerian Dwarf goats

Valencia-Posadas Mauricio,Lechuga-Arana Alma Arianna,Ávila-Ramos Fidel,Shepard Lisa,Montaldo Hugo H. 아세아·태평양축산학회 2022 Animal Bioscience Vol.35 No.3

Objective: This study was conducted to estimate multi-trait genetic parameters for somatic cell score (SCS), milk yield and type traits in Nigerian Dwarf (ND) goats from the United States. Methods: Data from 1,041 ND goats in the United States with kiddings in 95 herds were used to estimate multi-trait genetic parameters for SCS, milk (MILK), fat (FAT), and protein (PROT) yields, and 14 type traits. An 18-trait mixed linear animal model for lactation mean SCS (Log2), MILK, FAT, PROT, and 14 type traits was applied. A factor analytic approach (FA1) in ASReml software was used to obtain convergence. Results: Averages for SCS were low (2.85±1.29 Log2), and were 314±110.6, 20.9±7.4, and 14±4.9 kg, respectively, for MILK, FAT, and PROT. Heritabilities for SCS, MILK, FAT, and PROT were 0.32, 0.16, 0.16, and 0.10, respectively. The highest heritabilities for type traits were for stature (0.72), teat diameter (0.49), and rump width (0.48), and the lowest estimates were for dairyness (0.003) and medial suspensory ligament (0.03). Genetic correlations of SCS with MILK, FAT, and PROT were positive but low (0.25, 0.18, and 0.23, respectively). Genetic and phenotypic correlations between MILK, FAT, and PROT were high and positive (≥0.66). Absolute values of genetic correlations involving SCS with type traits were generally low or no different from zero. Most of the phenotypic correlations involving SCS with type traits were low. No serious unfavorable genetic correlations between milk yield traits and SCS or between milk yield traits or SCS and type traits were found. Conclusion: Genetic variation exists in the ND breed for most studied traits. The development of selection programs based on these estimates may help accelerate favorable multitrait genetic changes in this breed. Objective: This study was conducted to estimate multi-trait genetic parameters for somatic cell score (SCS), milk yield and type traits in Nigerian Dwarf (ND) goats from the United States.Methods: Data from 1,041 ND goats in the United States with kiddings in 95 herds were used to estimate multi-trait genetic parameters for SCS, milk (MILK), fat (FAT), and protein (PROT) yields, and 14 type traits. An 18-trait mixed linear animal model for lactation mean SCS (Log2), MILK, FAT, PROT, and 14 type traits was applied. A factor analytic approach (FA1) in ASReml software was used to obtain convergence.Results: Averages for SCS were low (2.85±1.29 Log2), and were 314±110.6, 20.9±7.4, and 14±4.9 kg, respectively, for MILK, FAT, and PROT. Heritabilities for SCS, MILK, FAT, and PROT were 0.32, 0.16, 0.16, and 0.10, respectively. The highest heritabilities for type traits were for stature (0.72), teat diameter (0.49), and rump width (0.48), and the lowest estimates were for dairyness (0.003) and medial suspensory ligament (0.03). Genetic correlations of SCS with MILK, FAT, and PROT were positive but low (0.25, 0.18, and 0.23, respectively). Genetic and phenotypic correlations between MILK, FAT, and PROT were high and positive (≥0.66). Absolute values of genetic correlations involving SCS with type traits were generally low or no different from zero. Most of the phenotypic correlations involving SCS with type traits were low. No serious unfavorable genetic correlations between milk yield traits and SCS or between milk yield traits or SCS and type traits were found.Conclusion: Genetic variation exists in the ND breed for most studied traits. The development of selection programs based on these estimates may help accelerate favorable multitrait genetic changes in this breed.

Regional Differences in Efficacy, Safety, and Biomarkers for Second-Line Axitinib in Patients with Advanced Hepatocellular Carcinoma: From a Randomized Phase II Study

Kudo, Masatoshi,Kang, Yoon-Koo,Park, Joong-Won,Qin, Shukui,Inaba, Yoshitaka,Assenat, Eric,Umeyama, Yoshiko,Lechuga, Maria José,Valota, Olga,Fujii, Yosuke,Martini, Jean-Francois,Williams, J. Andr S. Karger AG 2018 Liver cancer Vol.7 No.2

<P><B><I>Background:</I></B> An unmet need exists for treatment of patients with advanced hepatocellular carcinoma (HCC) who progress on or are intolerant to sorafenib. A global randomized phase II trial (ClinicalTrial.gov No. NCT01210495) of axitinib, a vascular endothelial growth factor receptor 1-3 inhibitor, in combination with best supportive care (BSC) did not prolong overall survival (OS) over placebo/BSC, but showed improved progression-free survival in some patients. Subgroup analyses were conducted to identify potential predictive/prognostic factors. <B><I>Methods:</I></B> The data from this phase II study were analyzed for the efficacy and safety of axitinib/BSC in patients from Asia versus non-Asia versus Asian subgroups (Japan, Korea, or mainland China/Hong Kong/Taiwan) and predictive/prognostic values of baseline microRNAs and serum soluble proteins, using the Cox proportional hazards model. <B><I>Results:</I></B> Of 202 patients, 78 were from non-Asia and 124 from Asia (37 Japanese, 36 Korean, and 51 Chinese). No significant differences in OS were found between axitinib/BSC and placebo/BSC in non-Asians, Asians, or Asian subgroups. However, in an exploratory analysis, axitinib/BSC showed favorable OS in Asians, especially Japanese, when patients intolerant to prior antiangiogenic therapy were excluded from the data set. Axitinib/BSC was well tolerated by non-Asians and Asians alike. The presence of 4 circulating microRNAs, including miR-5684 and miR-1224-5p, or a level lower than or equal to the median protein level of stromal cell-derived factor 1 at baseline was significantly associated with longer OS in axitinib/BSC-treated Asians or non-Asians. <B><I>Conclusions:</I></B> Axitinib/BSC did not prolong survival over placebo/BSC in non-Asians, Asians, or Asian subgroups, but favorable OS with axitinib/BSC was observed in a subset of Japanese patients. A patient population that excludes sorafenib-intolerant patients might potentially be more suitable for clinical trials of new agents in advanced HCC. Since these results are very preliminary, further investigation is warranted. The potential predictive/prognostic value of several baseline microRNAs and soluble proteins identified in this study would require validation in prospective studies on a large cohort of patients.</P>

Phase II study of sunitinib as second-line treatment for advanced gastric cancer

Bang, Yung-Jue,Kang, Yoon-Koo,Kang, Won K.,Boku, Narikazu,Chung, Hyun C.,Chen, Jen-Shi,Doi, Toshihiko,Sun, Yan,Shen, Lin,Qin, Shukui,Ng, Wai-Tong,Tursi, Jennifer M.,Lechuga, Maria J.,Lu, Dongrui Ray,R Springer US 2011 Investigational new drugs Vol.29 No.6

<P><B>Summary</B></P><P><I>Purpose.</I> This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. <I>Experimental design</I>. Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life. <I>Results</I>. Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6–2.6 months) and median OS was 6.8 months (95% CI, 4.4–9.6 months). Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome. <I>Conclusions</I>. The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.</P>