90 research outputs found
Triple-negative breast cancer: Current perspective on the evolving therapeutic landscape
Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy
All-d-Enantiomer of β-Amyloid Peptide Forms Ion Channels in Lipid Bilayers
Alzheimer’s disease (AD) is the most common type
of senile
dementia in aging populations. Amyloid β (Aβ)-mediated
dysregulation of ionic homeostasis is the prevailing underlying mechanism
leading to synaptic degeneration and neuronal death. Aβ-dependent
ionic dysregulation most likely occurs either directly via unregulated
ionic transport through the membrane or indirectly via Aβ binding
to cell membrane receptors and subsequent opening of existing ion
channels or transporters. Receptor binding is expected to involve
a high degree of stereospecificity. Here, we investigated whether
an Aβ peptide enantiomer, whose entire sequence consists of d-amino acids, can form ion-conducting channels; these channels
can directly mediate Aβ effects even in the absence of receptor–peptide
interactions. Using complementary approaches of planar lipid bilayer
(PLB) electrophysiological recordings and molecular dynamics (MD)
simulations, we show that the d-Aβ isomer exhibits
ion conductance behavior in the bilayer indistinguishable from that
described earlier for the l-Aβ isomer. The d isomer forms channel-like pores with heterogeneous ionic conductance
similar to the l-Aβ isomer channels, and the d-isomer channel conductance is blocked by Zn2+, a known
blocker of l-Aβ isomer channels. MD simulations further
verify formation of β-barrel-like Aβ channels with d- and l-isomers, illustrating that both d- and l-Aβ barrels can conduct cations. The calculated
values of the single-channel conductance are approximately in the
range of the experimental values. These findings are in agreement
with amyloids forming Ca2+ leaking, unregulated channels
in AD, and suggest that Aβ toxicity is mediated through a receptor-independent,
nonstereoselective mechanism
Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer
PURPOSE: Fertility and pregnancy-related issues are highly relevant for young ( 64 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues. METHODS: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed. RESULTS: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively. CONCLUSION: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling
Probing Structural Features of Alzheimer’s Amyloid-β Pores in Bilayers Using Site-Specific Amino Acid Substitutions
Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection
<p>Abstract</p> <p>Background</p> <p>The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised.</p> <p>Methods</p> <p>In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM) from paired surgical specimens of human GCA.</p> <p>Results</p> <p>Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses.</p> <p>Conclusion</p> <p>These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.</p
Amyloid-β-Induced Ion Flux in Artificial Lipid Bilayers and Neuronal Cells: Resolving a Controversy
Disruption of Lateral Efferent Pathways: Functional Changes in Auditory Evoked Responses
The functional consequences of selectively lesioning the lateral olivocochlear efferent system in guinea pigs were studied. The lateral superior olive (LSO) contains the cell bodies of lateral olivocochlear neurons. Melittin, a cytotoxic chemical, was injected into the brain stem using stereotaxic coordinates and near-field evoked potentials to target the LSO. Brain stem histology revealed discrete damage to the LSO following the injections. Functional consequences of this damage were reflected in depressed amplitude of the compound action potential of the eighth nerve (CAP) following the lesion. Threshold sensitivity and N1 latencies were relatively unchanged. Onset adaptation of the cubic distortion product otoacoustic emission (DPOAE) was evident, suggesting a reasonably intact medial efferent system. The present results provide the first report of functional changes induced by isolated manipulation of the lateral efferent pathway. They also confirm the suggestion that changes in single-unit auditory nerve activity after cutting the olivocochlear bundle are probably a consequence of disrupting the more lateral of the two olivocochlear efferent pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41379/1/10162_2002_Article_3018.pd
Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies
Comment on ‘Failure of intravitreal bevacizumab in the treatment of choroidal metastasis’
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