Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast cancer and their prognostic value has not been well documented in Asians.</p> <p>Methods</p> <p>A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by centralized pathology review. The average follow-up of the patients was 53.4 months. Overall and disease-free survival by molecular subtypes of breast cancer were evaluated.</p> <p>Results</p> <p>The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and triple-negative subtypes were 48.6%, 16.7%, 13.7%, and 12.9%, respectively. The luminal A subtype was more likely to be diagnosed in older women (P = 0.03) and had a stronger correlation with favorable clinicopathological factors (smaller tumor size, lower histologic grade, and earlier TNM stage) than the triple-negative or HER2 subtypes. Women with triple-negative breast cancer had a higher frequency of family history of breast cancer than women with other subtypes (P = 0.048). The 5-year overall/disease-free survival percentages for the luminal A, luminal B, HER2, and triple-negative subtypes were 92.9%/88.6%, 88.6%/85.1%, 83.2%/79.1%, and 80.7%/76.0%, respectively. A similar pattern was observed in multivariate analyses. Immunotherapy was associated with improved overall and disease-free survival for luminal A breast cancer, but reduced disease-free survival (HR = 2.21, 95% CI, 1.09-4.48) for the HER2 subtype of breast cancer.</p> <p>Conclusions</p> <p>The triple-negative and HER2 subtypes were associated with poorer outcomes compared with the luminal A subtype among these Chinese women. The HER2 subtype was more prevalent in this Chinese population compared with Western populations, suggesting the importance of standardized HER2 detection and anti-HER2 therapy to potentially benefit a high proportion of breast cancer patients in China.</p

Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Praziquantel has been used as first-line drug for chemotherapy of schistosomiasis since 1984. Besides praziquantel, artemether and artesunate have also been used for the control of this infectious disease since late 1990s. In this article, we conducted a systematic review and meta-analysis to evaluate the antischistosomal efficacy of different medication strategies including monotherapy or combination therapies of these drugs.</p> <p>Results</p> <p>A number of 52 trials from 38 articles published in peer-reviewed journals before July 2011 were selected for analysis after searching the following literature databases: the Cochrane Library, PubMed/Medline, ISI Web of Science, Chinese Biomedicine Literature Database, and China National Knowledge Infrastructure. Our meta-analyses showed that a dosage of 30-60 mg/kg praziquantel compared with placebo produced a protection rate of about 76% (95% CI: 67%-83%) for treating human schistosomiasis, which varied from 70% to 76% with no significant differences among the subspecies <it>S. haematobium</it>, <it>S. japonicum </it>or <it>S. mansoni</it>. Protection rates were higher when praziquantel doses were elevated, as concluded from the nRCTs results: the protection rate of praziquantel at 40 mg/kg was 52% (95% CI: 49%-55%), and it increased to 91% (95% CI: 88%-92%) when the dosages were elevated to 60/80/100 mg/kg divided two or more doses. Multiple doses of artemether or artesunate over 1- or 2-week intervals resulted in protection rates of 65% to 97% for preventing schistosomiasis, and increased doses and shorter medication intervals improved their efficacies. Praziquantel and artemisinin derivatives (artemether or artesunate) in combination resulted in a higher protection rate of 84% (95% CI: 64%-91%) than praziquantel monotherapy for treatment. praziquantel and artesunate in combination had a great protection rate of 96% (95% CI: 78%-99%) for preventing schistosomes infection.</p> <p>Conclusions</p> <p>According to the results, praziquantel remains effective in schistosomiasis treatment, and multiple doses would improve its efficacy; meanwhile, praziquantel is also a good drug for preventing acute schistosomiasis morbidity. It's better to use multiple doses of artemether or artesunate with 1- or 2-week intervals for prevention against schistosome infection. Praziquantel and artemether or artesunate in combination perform better in treatment than praziquantel monotherapy, and they are especially suitable for treating the patients with repeated exposure to infected water.</p

Evaluation of the clinical and analgesic effects of subarachnoid ketamine-lidocaine administration in goats undergoing mastectomy

Mousa Daradka, Zuhair Bani IsmailDepartment of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, JordanAbstract: Twenty adult female goats affected with chronic mastitis were subjected to mastectomy or hemimastectomy under subarachnoid regional analgesia using a ketamine-lidocaine combination. Ketamine at 1.5 mg/kg and lidocaine hydrochloride at 1.25 mg/kg were administered intrathecally at the lumbosacral intervertebral space. Goats were then subjected to a 120-minute observation period for systemic or neurotoxic symptoms such as agitation, restlessness, hind limb paralysis, or seizures. In addition, analgesia of the caudal abdominal region and signs of systemic sedation were scored on a scale of 0&ndash;3. Heart rate, respiratory rate, and rectal temperature were also recorded prior to (baseline values) and at 5, 15, 30, 60, 90, and 120 minutes after administration. Mastectomy or hemimastectomy operation was carried out after full assurance of the analgesic effect on the udder and caudal abdominal region. Time of onset of surgical analgesia (score 3) was achieved at 15 minutes and lasted for 60 minutes. Maximal sedation score was recorded at 15 minutes and lasted for 60 minutes, then decreased thereafter, with the lowest sedation score recorded at 120 minutes. There was a significant (P&lt;0.05) rise in heart rate at some point between 5&ndash;90 minutes, while the respiratory rate and rectal temperature did not change significantly from baseline values. Postoperatively, animals did not show any signs of pain or discomfort. Follow-up on the operated goats showed that all wounds were fully healed without any significant complications. In goats, intrathecal administration of ketamine-lidocaine combination resulted in a safe and effective analgesia of the caudal abdominal and udder region sufficient to perform mastectomy or hemimastectomy.Keywords: analgesia, sedation, ruminants, mastectom

Pharmacokinetic evaluation of D-ribose after oral and intravenous administration to healthy rabbits

Karem H Alzoubi,1 Zuhair Bani Ismail,2 Mohamed K AL-Essa,3 Osama Y Alshogran,1 Reem F Abutayeh,4 Nareman Abu-Baker5 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Physiology, Faculty of Medicine, University of Jordan, Amman, Jordan; 4Department of Medicinal Chemistry and Phytochemistry, Applied Science Private University, Amman, Jordan; 5Philadelphia Biomedical Products Development Center, Amman, Jordan Introduction: This study explored d-ribose pharmacokinetics after intravenous (IV) and oral administration to healthy rabbits. Materials and methods: D-ribose was administered once as 420 mg/kg (N=4) or 840 mg/kg (N=6) dose intravenously, or as an oral dose of 420 mg/kg (N=3) or 840 mg/kg (N=3). Serum was obtained at various time points, up to 210 minutes after administration. Urine was also collected after IV administration. Pharmacokinetic parameters were determined from drug concentration&ndash;time data using Kinetica software. Results: The findings showed that D-ribose follows a dose-dependent kinetic profile. With doubling the IV dose, AUCtotal was significantly increased by threefold, while the clearance was decreased by 44%. The half-life was 1.7-fold longer at the higher dose. Similar nonsignificant trends were also observed at oral administration. D-ribose was rapidly absorbed (Tmax=36&ndash;44 minutes) and rapidly disappeared from plasma (within &lt;140 minutes). Additionally, D-ribose was partially (18&ndash;37.5%) recovered from urine. Conclusion: Collectively, D-ribose showed a dose-dependent kinetic profile, where parameters change according to dosing levels. D-ribose clearance seems to follow first-order kinetics at low dose. Thereafter, elimination systems are saturated, and elimination continues in a fast manner. Urine recovery was partial, which could be attributed to the several metabolic pathways that pentose can undergo. Keywords: D-ribose, single dose, pharmacokinetics, rabbits, oral, intravenou