Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant tamoxifen alone: patterns of recurrence

Purpose: To determine the patterns, incidence and risk factors for local-regional recurrence in patients with Stage II and III breast cancer treated with adjuvant tamoxifen alone, without adjuvant radiation.Material and Methods: The records of patients referred to the London Regional Cancer Centre with a diagnosis of breast cancer between 1980–1989 were reviewed. During this time period, it was the policy of the institution to omit local-regional radiation to patients receiving adjuvant systemic therapy. One hundred and fifty axillary node-positive Stage II and III breast cancer patients received adjuvant tamoxifen alone without postoperative local-regional radiation; these patients form the basis of this report.Results: Median follow-up was 67 months for the entire patient group and 85 months for the living patients. During this time, 42% of patients developed a recurrence, 22% first recurred in local-regional sites. The total incidence of local-regional recurrence (including those patients who first relapsed with systemic metastases) was 30%. Of the segmental mastectomy patients, 13% had recurrences in the intact breast. Of the modified radical mastectomy patients, 10% developed chest wall recurrences. Five percent of recurrences were first in the axilla and 6% in the supraclavicular nodes. Five-year actuarial survival for the entire patient group was 79% and disease-free survival was 60%, with a median disease-free survival time of 87 months. Five-year local-regional relapse-free survival was 76%. Five-year local-regional relapse-free survival was < 76% for those patients with 4 or more positive axillary nodes, regardless of tumor size. On univariable analysis, positive resection margins, number of positive axillary nodes, menopausal status, and negative estrogen and progesterone receptors were significant for isolated local-regional recurrence. On multivariable analysis, only positive resection margins and negative receptors remained significant. In terms of regional recurrence specifically, negative estrogen and progesterone-receptor status and positive resection margins were, again, prognostically significant.Conclusions: Postmenopausal women receiving adjuvant tamoxifen who have positive resection margins, ≥ 4 positive axillary nodes and/or negative estrogen and progesterone receptors, are at higher risk of local and regional recurrence and should, therefore, receive local-regional radiation.     

Current trends in the study of potassium channel openers

Some eight years ago it was found that certain smooth muscle relaxants exert their effect by opening a specific K⁺ channel resulting in cell membrane hyperpolarization. The use of K⁺channel openers (cromakalim, pinacidil and RP-52891) and compounds which antagonize their actions (glibenclamide, phentolamine and alinidine) has enabled a great deal of research to be performed into the role of this K⁺ channel, not only in smooth muscle, but also in cardiac and skeletal muscle as well as neural and endocrine organ function. Much of the attention has centred on the smooth muscle relaxant actions of the K⁺ channel openers, since they have potential therapeutic use in disorders involving smooth muscle over-reactivity such as hypertension and asthma. More recently the cardiac actions of the K⁺ channel openers have become the focus of interest. Although there appear to be good theoretical reasons why K⁺ channel openers may be of use in some arrhythmias and in ischaemic heart disease there are major hurdles to overcome. In particular, given that the effect of these compounds on vascular smooth muscle occurs at a concentration 20- to 100-fold lower than that required to produce cardiac effects, it is likely their therapeutic usefulness will be limited until a breakthrough in cardiac/vascular selectivity is made. There is also growing interest in endogenous K⁺ channel openers and the physiological role of the K⁺ channel which they open. Opening of K⁺ channels, either spontaneously or by endogenous regulators, could possibly be an important hypotensive mechanism both under normal conditions and in a number of pathological conditions. Research into these areas will need to continue if the true therapeutic potential of K⁺ channel openers and their antagonists are to be realized.     

Association between Baseline SBP/DBP and All-Cause Mortality in Residents of Shanxi,China: A Population-based Cohort Study from 2002 to 2015

Objective To investigate the association between blood pressure and all-cause mortality in Shanxi,China.Methods The‘2002 China Nutrition and Health Survey’baseline data in Shanxi province was used.A retrospective investigation was performed in 2015.The effects of SBP and DBP on the all-cause mortality were analyzed using the Cox regression model.The hazard ratio(HR)and 95%confidence interval(CI)were estimated by the sex and age groups.Results The follow-up rate was 76.52%over 13 years,while the cumulative mortality rate for all participants was 917.12/100,000 person-years.The mortality rose with an increasing SBP(χ_trend²=270.537,P<0.001)or DBP level(χ_trend²=57.240,P<0.001).After adjustment for the confounding factors,a significant association between mortality and high SBP(≥160 mm Hg)and high DBP(≥100 mm Hg),with adjusted HR ranging from 1.405-to 2.179-fold for SBP and 1.550-to 2.854-fold for DBP,was noted.Significant HRs for most DBP subgroups were found in>60-year-old participants.Males with DBP≥100 mm Hg had a significantly higher mortality,with an HR(95%CI)of 2.715(1.377–5.351).Conclusion Adults with SBP>160 mm Hg and DBP>100 mm Hg had a higher mortality risk.Sex and age difference was noted in both DBP and mortality risk.     

miR‐423‐3p activates FAK signaling pathway to drive EMT process and tumor growth in lung adenocarcinoma through targeting CYBRD1

BackgroundLung adenocarcinoma (LUAD) is a malignant tumor with a high fatality rate and poor overall survival, while molecular targets diagnosing and alleviating lung cancer remain inadequate.MethodsIn this article, we highlighted the upregulation of microRNA‐423‐3p (miR‐423‐3p) in LUAD, especially in smokers aged over 40, and revealed that the high expression of miR‐423‐3p was significantly associated with smoker, age, and pathologic stage of LUAD patients.ResultsMoreover, overexpressing miR‐423‐3p could facilitate LUAD cell proliferation, invasion, adhesion, and epithelial–mesenchymal transition (EMT) process, while depleted miR‐423‐3p caused repressive influence upon it. Mechanically, we identified that miR‐423‐3p could activate FAK signaling pathway through binding to the 3''‐UTR of cytochrome B reductase 1 (CYBRD1). Furthermore, we demonstrated that CYBRD1 was lowly expressed in LUAD, and miR‐423‐3p overexpression could rescue the impairment of LUAD cell proliferation, invasion, adhesion, and EMT caused by CYBRD1 depletion. Noticeably, miR‐423‐3p depletion efficiently hindered LUAD tumor growth in vivo.ConclusionCollectively, our findings demonstrated that miR‐423‐3p/CYBRD1 axis could be regarded as a promising biomarker to alleviate the poor LUAD prognosis.     

An automated intelligent diagnostic system for the interpretation of umbilical artery Doppler velocimetry

The objective is to develop an automated intelligent diagnostic system for the interpretation of umbilical artery velocity waveforms. An ultrasound instrument with pulsed-wave Doppler is connected to a microcomputer by means of a frame grabber. After data acquisition, umbilical Doppler velocimetry is handled as a pattern recognition (feature extraction and classification) and decision-making problem. Automated image processing (enhancement, smoothing/thresholding and edge detection) and analysis are used for feature extraction. Six waveform indices obtained by feature extraction are used as input layer to vector quantization which classifies waveforms into six groups. A clinical decision is assigned to each group by the medical expert. Our system is trained by 278 and 380 waveform images of 94 normal and 157 high risk pregnancies, respectively. The system was tested with 193 and 61 images of normal and risky pregnancies; it was demonstrated that sensitivity and specificity of the system are 54.1% and 80.3%, respectively.     

Increased levels of soluble triggering receptor expressed on myeloid cells-1 in cerebrospinal fluid of subarachnoid hemorrhage patients

Triggering receptor expressed on myeloid cells-1 (TREM-1) has been highlighted as a key amplifier of inflammatory response in various diseases. To determine the contribution of TREM-1 in the inflammatory cascade after subarachnoid hemorrhage (SAH), concentrations of soluble TREM-1 (sTREM-1) in cerebrospinal fluid (CSF) from 30 SAH patients and 9 healthy volunteers were measured by enzyme-linked immunosorbent assay. It was shown that the CSF sTREM-1 levels of SAH patients increased significantly than that of the volunteers (P < 0.05). Interestingly, the levels were up-regulated dynamically over time with an early increase within 2 days and a late peak at day 6 after SAH onset. In addition, it was found that the early sTREM-1 levels (within 3 days post-SAH) were negatively correlated with Glasgow Coma Scale (r = −0.550, P = 0.022) and positively correlated with the Hunt and Hess scale (r = 0.603, P = 0.010) respectively conducted on admission, also the early sTREM-1 levels were negatively correlated with Glasgow Outcome Scale (r = −0.505, P = 0.039) and positively correlated with modified Rankin Scale (r = 0.557, P = 0.020) respectively conducted one month after SAH. Altogether, this is the first study showing CSF sTREM-1 dynamics in SAH patients, and exploring the correlations of early CSF sTREM-1 levels to patients’ severity and prognosis, which suggests that TREM-1 may play an important role in the inflammatory cascade after SAH and act as a monitoring biomarker facilitated to assess the severity and prognosis of SAH patients.