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"J -P Chen"
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A Five-Gene Signature and Clinical Outcome in Non–Small-Cell Lung Cancer
The authors show that a five-gene signature is closely associated with outcome among patients who have undergone surgical resection of early-stage non–small-cell lung cancer. This investigation represents the final phase of work to devise molecular methods for staging tumors and formulating a prognosis. For the findings to be clinically directive, these kinds of signatures will need to be incorporated into prospective clinical trials of cancer treatment.
The authors show that a five-gene signature is closely associated with outcome among patients who have undergone surgical resection of early-stage non–small-cell lung cancer.
Lung cancer — predominantly non–small-cell lung cancer (NSCLC) — is the most common cause of death from cancer worldwide.
1
The relapse rate among patients with early-stage NSCLC is 40% within 5 years after potentially curative treatment.
2
The current staging system for NSCLC is inadequate for predicting the outcome of treatment.
Gene-expression profiling (see Glossary) by means of microarrays
3
,
4
and reverse-transcriptase polymerase chain reaction (RT-PCR)
5
,
6
is useful for classifying tumors and formulating a prognosis for patients with various types of cancer,
7
–
9
including lung cancer.
10
–
16
The use of microarrays in clinical practice is limited, however, by the large . . .
Journal Article
Intracellular hydrogelation preserves fluid and functional cell membrane interfaces for biological interactions
Cell membranes are an intricate yet fragile interface that requires substrate support for stabilization. Upon cell death, disassembly of the cytoskeletal network deprives plasma membranes of mechanical support and leads to membrane rupture and disintegration. By assembling a network of synthetic hydrogel polymers inside the intracellular compartment using photo-activated crosslinking chemistry, we show that the fluid cell membrane can be preserved, resulting in intracellularly gelated cells with robust stability. Upon assessing several types of adherent and suspension cells over a range of hydrogel crosslinking densities, we validate retention of surface properties, membrane lipid fluidity, lipid order, and protein mobility on the gelated cells. Preservation of cell surface functions is further demonstrated with gelated antigen presenting cells, which engage with antigen-specific T lymphocytes and effectively promote cell expansion ex vivo and in vivo. The intracellular hydrogelation technique presents a versatile cell fixation approach adaptable for biomembrane studies and biomedical device construction.
Cell membrane interface is mostly studied using synthetic bilayers and reconstituted cell membranes. Here the authors present a new cell fixation method in which the cytoskeleton is replaced by a synthetic hydrogel polymer network assembled inside the cell, thereby preserving the fluid membrane properties after cell death.
Journal Article
Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases
The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the
HOX11
expression represented a favorable prognostic factor as it was in adult ones. We identified
CRLF2
overexpression as an intermediate-risk marker and
Ik6
variant of
IKZF1
gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that
Ik6
variant and
CRLF2
overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.
Journal Article
Tumor microenvironment-based screening repurposes drugs targeting cancer stem cells and cancer-associated fibroblasts
The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME.
Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs
and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics.
patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs.
The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity
and
, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs.
The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.
Journal Article
A garden called home
\"A little girl goes to her mother's homeland and develops an appreciation for nature. Returning to Canada she plants a garden that represents both sides of her heritage as Taiwanese plants grow side-by-side with Canadian wildflowers.\"-- Provided by publisher.
Book
Effects of Exercise Alone or in Combination with High-Protein Diet on Muscle Function, Aerobic Capacity, and Physical Function in Middle-Aged Obese Adults: A Randomized Controlled Trial
Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults.
Sixty-nine middle-aged (501–64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a highprotein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention.
After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test).
For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.
Journal Article