A hypo-osmotically induced increase in intracellular Ca2+ in lactating mouse mammary epithelial cells involving Ca2+ influx

 Using a fluorescent Ca²⁺-sensitive dye, we studied the effect of hypo-osmotic stress on the intracellular free Ca²⁺ concentration ([Ca²⁺]_i) in acini freshly isolated from lactating mouse mammary gland. The basal [Ca²⁺]_i of mammary acini was unaffected by a 50% (v/v) dilution of suspensions with isotonic or hypertonic buffer, or after ionic (iso-osmotic) dilution (external Ca²⁺ was 3 mM). Hypo-osmotic dilution (50%) elicited a rapid increase in [Ca²⁺]_i comprising a large, transient elevation, followed by a maintained plateau phase. No hypo-osmotically induced rise in [Ca²⁺]_i was observed in the absence of extracellular Ca²⁺. Neither microtubule disassembly using nocodazole nor actin disruption with cytochalasin D prevented hypo-osmotically evoked stimulation of [Ca²⁺]_i. Pre-incubation of acini with nifedipine did not prevent hypo-osmotically induced stimulation of [Ca²⁺]_i, whereas a non-specific cation channel blocker, gadolinium, partially inhibited the increases in [Ca²⁺]_i induced by hypo-osmotic stress. Furthermore, the transient component was still apparent, and not diminished in magnitude, after [Ca²⁺]_i had been elevated by mobilisation of Ca²⁺ from intracellular stores using thapsigargin. The results demonstrate that hypo-osmotic stress generates an increase in [Ca²⁺]_i in lactating mammary epithelial cells, the major, transient component of which appears to be due to influx of extracellular Ca²⁺. Received: 15 October 1996 / Received after revision and accepted: 1 November 1996     

The 2P-domain K+ channels: role in apoptosis and tumorigenesis

Two-pore (2P)-domain K⁺ channels have been shown recently to play a critical role in both cell apoptosis and tumorigenesis. The activity of two-pore, (TWIK)-related acid-sensitive-3 (TASK-3) K⁺ channels, is responsible for K⁺-dependent apoptosis of cultured cerebellar granule neurons. Neuron death can be prevented by conditions that specifically reduce K⁺ efflux through the TASK-3 channels. Moreover, genetic transfer of TASK subunits into hippocampal neurons that lack TASK-3, induces apoptosis. These results indicate a direct link between TASK K⁺ channel activity and the physiological process of programmed cell death. The TASK-3 K⁺ channel gene has also been shown to be amplified genomically and over-expressed in a significant number of breast tumours. TASK-3 has a potent oncogenic potential that appears to be related directly to its K⁺ channel function. In the present review, we will examine the pro-apoptotic and oncogenic properties of TASK-3. We will discuss: (1) the molecular and functional properties of the novel family of mammalian 2P domain K⁺ channels; (2) the role of TASK-3 in cerebellar granule neuron apoptosis and (3) the role of TASK-3 in breast tumorigenesis.     

Studies on the mammary tumor-inhibiting effects of diethylstilbestrol and its mono- and diphosphate

Summary Diethylstilbestrol (DES), diethylstilbestrol monophosphate (DES-MP) and diethylstilbestrol diphosphate (DES-DP) were tested for their estrogen receptor affinity, estrogenic potency and mammary tumor-inhibiting activity in vitro and in vivo. DES had a much higher receptor binding affinity than its mono-or diphosphate. All three compounds inhibited the growth of the hormone-dependent MCF-7 and hormone-independent MDA-MB 231 breast cancer line only at relatively high concentrations. The estrogenic potency in the immature mouse uterine weight test decreased in the order DES>DES-MPDES-DP. The hormone-dependent MXT mammary tumor of the mouse was inhibited by all three compounds at a dosage of 1.0 mg/kg per week. At a dose of 0.01 mg/kg, DES, DES-MP, and DES-DP stimulated the tumor growth. Thus, for the first time, a biphasic effect on tumor growth was demonstrated in intact mature animals. As the effects of all three compounds were similar in this assay, a cleavage of the phosphate groups is likely. A decrease in estrogenic potency concomitant with a retained antitumor effect of DES-MP and DES-DP compared to DES was not demonstrable in the mature mouse using the MXT assay, only in the uterotrophic test in the immature mouse.Dedicated to Professor Dietrich Schmähl on occasion of his 60th birthdaySupported by the Deutsche Forschungsgemeinschaft and by the Verband der Chemischen Industrie, Fonds der Chemischen Industrie. The authors thank Dr. Weigert, Asta-Werke AG, Degussa Pharma Gruppe, Bielefeld, FRG, for the analysis of DES-MP and DP     

Dysplasia in the gastrointestinal tract: definition and clinical significance

Summary The term dysplasia is used increasingly in gastrointestinal pathology. Dysplasia denotes an unequivocal neoplastic epithelial alteration without invasive growth and is synonymous with the term intraepithelial neoplasia. Dysplasia is the paradigm of a precancerous lesion. Confusion arises because some pathologists do not use the term in the above-defined sense but to describe regenerative, inflammatory and reactive changes. It is essential to separate these kinds of non-neoplastic epithelial changes from neoplastic dyplasia because the clinical consequences are completely different. The general morphology and the grading of dysplasia are described. Most dysplasias in the gastrointestinal tract are the polypoid lesion; dysplasias in flat mucosa are uncommon. Knowledge of the incidence of dysplasia in the gastrointestinal tract is important for the concept of secondary cancer prevention.     

中文版感知社会支持量表在老年癌症患者中的信效度分析

目的 检验中文版感知社会支持量表（the multidimensional scale of perceived social support, MSPSS）在老年癌症患者中应用的信效度。方法 采用整群抽样的方法,使用中文版感知社会支持量表对老年癌症患者进行调查,并对结果进行信效度检验。结果 共收到有效问卷520份,中文版感知社会支持量表的Cronbach α系数为0.877;探索性因子中共提取出公因子3个,累积方差贡献率为69.5%;通过验证性因子分析得出GFI、CFI、IFI指标范围在0.855～0.921之间。结论 中文版社会支持量表在老年癌症患者中应用具有良好的信效度,可用于评估该人群感知社会支持水平。     

Epidemiological link between obesity,type 2 diabetes mellitus and cancer

There exists a complex interaction between obesity, type 2 diabetes mellitus (T2DM) and cancer, and an increase in the incidence of cancer is expected with the growing obesity-diabetes pandemic. The association of cancer with diabetes mellitus and obesity appears to be site-specific, the highest risk being for post-menopausal breast cancer, endometrial cancer, and colorectal cancer. Moreover, there is worsening of hyperglycaemia with the onset of cancer, evidencing a bi-directional link between cancer and diabetes mellitus and the need for monitoring for diabetes in cancer survivors. In this review, we look at the epidemiological evidence from observational studies and Mendelian randomization studies linking obesity, diabetes, and cancer, as well as the complex pathophysiological mechanisms involved, including insulin resistance with associated hyperinsulinaemia, the effect of chronic low-grade inflammation, and the effect of various adipokines that are associated with obesity and T2DM. Additionally, we describe the novel therapeutic strategies, based on their role on the discrete pathophysiological mechanisms involved in the tumourigenesis.     

Neighbourhood migrant composition and tobacco-related cancer mortality: A census-linked study among five origin groups in urban Belgium

We studied the role of ‘ethnic density’ in the neighbourhood for tobacco-related cancer mortality among five migrant origin groups in urban Belgium. Using full population linked census data, multilevel Poisson models were applied to model effects of three linear and categorical indicators of same-origin presence for each origin group, and to test effect mediation by migrant generation and educational level. We first of all found that increased same migrant-origin presence in the neighbourhood had protective effects on tobacco-related cancer mortality for men in most groups. Second, only Turkish men had a mortality disadvantage when Turkish concentration was higher. Third, effects were not detected across all indicators of same-origin presence, nor among most groups of women. Finally, for several groups, neighbourhood effects were mediated by generational status and educational level.     

Re-grounding the concept of liminality by foregrounding spatial aspects in experiences of cancer care

Liminality captures the passing stages in transitioning from one sociocultural status to another. As its spatial dimension remains under-examined, we analyse this in experiences of people affected by cancer. We review liminality in cancer-related literature and juxtapose this with empirical material. Analysing interview data (with eight patients) and participant-made photos highlights why places may be experienced differently throughout a period of illness and how places of diagnosis and care ‘stretch’ across locations. We conclude that exploring liminality's spatial dimension has implications for people ‘living beyond’ cancer, advances sociological understandings of (cancer) illness, and may inform healthcare facility design.     

多学科协作诊疗助力直肠癌手术质量提升

目的探讨多学科协作诊疗在直肠癌手术中的开展成效。方法将进入多学科协作的患者和未进入多学科协作的患者分别设为观察组和对照组,通过多项指标量化分析直肠癌多学科协作开展成效。结果观察组的术后住院时长短于对照组,差异有统计学意义（P<0.05）;术后首次下床时间短于对照组,差异有统计学意义（P<0.05）;手术总费用、检查费、床位费少于对照组,差异有统计学意义（P<0.05）。观察组低位直肠癌手术有效保肛率高于对照组;在术后早期并发症中,观察组病例数少于对照组;在Ⅲ期直肠癌患者术后无进展生存时间上,观察组要高于对照组,差异有统计学意义（P<0.05）。观察组在生存量表总分、生理领域、心理领域得分均高于对照组,差异有统计学意义（P<0.05）。结论多学科协作在直肠癌诊疗中效果明显,能够确保直肠癌患者手术安全,缩短术后住院时长,降低手术费用,并减少术后并发症发生率,提升低位直肠癌有效保肛率,延长Ⅲ期直肠癌患者术后无进展生存时间,改善患者生存质量。