PRL3-zumab, a first-in-class humanized antibody for cancer therapy

Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated with shortened overall survival of GC patients. PRL-3 protein was overexpressed in 85% of fresh-frozen clinical gastric tumor samples examined but not in patient-matched normal gastric tissues. Using human GC cell lines, we demonstrated that PRL3-zumab specifically blocked PRL-3(+), but not PRL-3(–), orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3(+) tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become “extracellular oncotargets” that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells. In summary, our results document a comprehensive cancer therapeutic approach to specific antibody-targeted therapy against the PRL-3 oncotarget as a case study for developing antibodies against other intracellular targets in drug discovery

A comparison of collaborative and individualistic problem solving in younger and older adults on an everyday task.

Researchers examining everyday problem solving in adulthood have focused mainly on age differences in performance (e.g., Denney & Palmer, 1981). Older adults are often found to be poor problem solvers in comparison to younger adults because older adults use problem-solving strategies that are defined as less effective by researchers. Furthermore, researchers have focused on problem solving as a solitary activity and not as a collaborative activity. In addition, the problem-solving tasks researchers have used to measure everyday problem solving often resemble traditional problem-solving tasks. Thus, attention should be directed toward comparing younger and older adults on ecologically valid collaborative problem-solving tasks to determine whether age differences are found. The present study examined individual and collaborative problem-solving performance in younger and older adults on an everyday problem-solving task, a cross country trip-planning task. Younger adults (24 females, 23 males; M age = 20.43, SD = 1.43) and older adults (24 males, 24 females; M age = 70.95, SD = 6.67) participated in the study. Performance on the task was measured by assessing the percentage of the four required tasks participants completed accurately (wedding, city, national park, Mt. Rushmore), and number of calculation errors, task-completion time, and route efficiency. Participants who collaborated with their friend on the everyday problem-solving task did not outperform participants who completed the task alone, Age differences favoring younger adults were found on three performance measures. Younger adults completed more of the complex requirements (city, Mt. Rushmore), and also completed the task faster than older adults. Significant differences between younger and older adults were not found on the other measures of performance such as the two aspects of the task most stressed in the task (attending the wedding and routing the most time efficient trip). Age differences also were not found in the choice component of the task (national park completion) or the number of calculation errors. Age, math, education, and problem-solving condition predicted aspects of task performance. The results of the study suggest that everyday problem solving may differ from traditional problem solving. Age differences that are often found on traditional problem-solving tasks may not be as apparent on everyday problem solving tasks

Friendship, Gender, and Preadolescents\u27 Representations of Peer Collaboration

The experience of collaboration from preadolescents’ perspectives was examined as a function of dyad gender and degree of friendship. Sixth graders (11–13 years, mostly White and middle class) worked within same- and other-gender dyads (18 girl, 17 boy, 17 mixed-gender) of varying degrees of friendship on a 4-week-long creative writing task at school. Enjoyment expectations and affiliation perceptions were greater in dyads with greater degrees of friendship, and in same-gender dyads as compared with mixed-gender dyads. More positive enjoyment expectations and greater perceived affiliation, agreement, and influence were related to better task performance. Implications of these results for understanding the social context of collaboration from peer partners’ perspectives and successful classroom collaborations are discussed

Targeting breast stem cells with the cancer preventive compounds curcumin and piperine

International audienceThe cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 mu M and completely at 10 mu M concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 mu M and completely at 10 mu M. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials

Cloth-Based Power Shirt for Wearable Energy Harvesting and Clothes Ornamentation

Harvesting ambient mechanical energy from human body motion has attracted great research interest. In this work, a power shirt based on triboelectrification and the electrostatic induction effect between fluorinated ethylene propylene (FEP) and external objects is demonstrated. This power shirt can effectively convert the ambient mechanical energy into electric power, and the working mechanism is systematically discussed. A maximum short-circuit current density of ∼0.37 μA/cm² and a maximum peak power density of ∼4.65 μW/cm² were achieved. Simultaneously, 11 blue LEDs were lit by sliding the sleeve and power shirt, indicating the potential application of the power shirt in clothes ornamentation and risk warning. This study develops an efficient path for harvesting human body energy and promoting the development of wearable electronics and smart garments

Cloth-Based Power Shirt for Wearable Energy Harvesting and Clothes Ornamentation

Harvesting ambient mechanical energy from human body motion has attracted great research interest. In this work, a power shirt based on triboelectrification and the electrostatic induction effect between fluorinated ethylene propylene (FEP) and external objects is demonstrated. This power shirt can effectively convert the ambient mechanical energy into electric power, and the working mechanism is systematically discussed. A maximum short-circuit current density of ∼0.37 μA/cm² and a maximum peak power density of ∼4.65 μW/cm² were achieved. Simultaneously, 11 blue LEDs were lit by sliding the sleeve and power shirt, indicating the potential application of the power shirt in clothes ornamentation and risk warning. This study develops an efficient path for harvesting human body energy and promoting the development of wearable electronics and smart garments