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PITTSBURGH, July 26, 2021 - Adolescents who set goals for their future and those with strong parental support are less likely to use e-cigarettes and other tobacco products, according to a study by UPMC Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine physician-scientists.

The research, published today in the journal Pediatrics, suggests that strategies to prevent youth vaping may be different from what works to dissuade youth from smoking cigarettes.

"The use of e-cigarettes by young people is at epidemic proportions, with 27% of youth surveyed saying they'd vaped in the last 30 days," said lead author Nicholas Szoko, M.D., a fellow in the Division of Adolescent and Young Adult Medicine at UPMC Children's. "And a lot of the traditional methods we think of for counseling youth on the dangers of tobacco and drug use may not apply to vaping. Pediatricians and parents need a better understanding of what motivates adolescents to eschew e-cigarettes."

Szoko and his colleagues analyzed anonymous questionnaires administered in partnership with the Allegheny County Health Department and completed by 2,487 high school students in Pittsburgh Public Schools. The surveys asked questions to ascertain if and how often the students used e-cigarettes or other tobacco products, and to determine if any of four "protective factors" validated by previous research were associated with a lower likelihood of vaping or smoking.

The protective factors examined were:

Future orientation: A person's beliefs, hopes and goals related to the future.

Parental monitoring: Parent-child interactions and communication.

Social support: The ability to rely on friends and peers.

School connectedness: A sense of belonging and inclusion at school.

In the study, positive future orientation and high levels of parental monitoring were both linked with a 10% to 25% lower prevalence of recently or ever vaping, compared to peers with lower scores on those protective factors. There was no link between social support or school connectedness and use of e-cigarettes.

All four protective factors were associated with lower prevalence of smoking or use of other tobacco products, but none were linked to intent to quit using tobacco products. This suggests that once young people begin to use tobacco, quitting may be more difficult to promote. The researchers note that these findings should be explored to develop improved youth tobacco prevention efforts, but that it isn't surprising that the results for vaping weren't exactly the same as for smoking.

"E-cigarettes are positioned and marketed differently than tobacco cigarettes. They've been popularized as tools for smoking cessation, and previous research has found the various flavors and trendy ads for vaping are attractive to youth," said Szoko. "We also know that vaping primes adolescents to transition to smoking cigarettes and other substance use. So, it stands to reason that we may need different approaches to keep kids from vaping, than we use to stop them from smoking."

Senior author Alison Culyba, M.D., Ph.D., M.P.H., assistant professor of pediatrics, public health, and clinical and translational science at Pitt, noted that frameworks already exist to help clinicians use future orientation and encourage parental monitoring when providing health care to young people, which bodes well for developing e-cigarette intervention programs to strengthen these protective factors.

"Future orientation is something very tangible that pediatricians and other health care providers can talk with teens about in the clinic--motivational interviewing is something we're very comfortable doing with our patients," said Culyba, also an adolescent medicine physician and director of the Empowering Teens to Thrive program at UPMC Children's. "And we can help parents to navigate their roles as their children become pre-teens and teens, and help encourage open conversations with their kids about what they're encountering."

Oncotarget published "TERT and its binding protein: overexpression of GABPA/B in high grade gliomas" which reported that all GA-binding proteins progress through the glioma grades and have the highest expression levels in secondary glioblastomas.

In secondary glioblastomas after chemotherapy, GABPB1 and GABPB1-L are expressed on a lower level than without treatment.

Between primary and secondary glioblastomas with and without chemotherapy, TERT is elevated in the former while GABPB1 is increased in the secondary glioblastomas.

GABPA and GABPB1, GABPB1-L and GABPB1-S positively correlate in primary glioblastomas.

This Oncotarget study confirms the upregulation of TERT in primary glioblastomas while all GABP proteins rise with the malignancy of the gliomas.

This Oncotarget study confirms the upregulation of TERT in primary glioblastomas while all GABP proteins rise with the malignancy of the gliomas.

Dr. Marco Timmer from The University of Cologne said, "Gliomas are the most common primary tumors of the central nervous system (CNS)"

They comprise the diffuse astrocytomas and oligodendrogliomas World Health Organization grade II, the anaplastic astrocytomas and oligondendrogliomas WHO grade III and also the most frequent one, the glioblastoma multiforme WHO grade IV.

These two point mutations occur frequently in tumor cells that do not need a continual regeneration such as melanomas and gliomas.

Among the gliomas, 83% of the primary glioblastomas harbor those hotspot mutations with a different distribution between C228T and C250T while in lower glioma grades they seem to be rare.

Recent studies showed that the GABP tetramer forming isoforms, especially GABPB1-L, activate the mutant TERT promoter and a disruption of B1L generates telomeric loss in glioblastoma cell lines introducing the importance of GABPA/B isoforms in the mutated TERT promoter dependent gliomas.

Consequently, in this study the authors investigated the mRNA expression level of TERT and all GABPA/B isoforms and their correlation and interplay in the grade II, grade III gliomas as well as in the primary and secondary glioblastomas to understand their role in the gliomagenesis.

The Timmer Research Team concluded in their Oncotarget Research Output that the two somatic mutations in the promoter region of TERT create a de novo binding motif for GABP .

The proof, that GABP is recruited to the hotspot mutations of the promoter, thus reactivating and inducing TERT expression in glioblastoma cell lines, gave a significant role to GABP as an transcription regulator in a TERT dependent manner and provides evidence of specific cancer interaction in the promoter core which may lead to limitless replication.

Secondary GBMs seem to have more than 80% of IDH1 mutations indicating the progression from diffuse gliomas and primary GBMs harbor fewer than 5% of IDH1 missense mutations and are identified as de novo tumors.

This research group is the first to present an upregulation of all GABP components in the different glioma grades and GABPA, -B1, -B1-L, -B1-S are gradually expressed during malignancy progression from lower to higher grade while the most expression is observed in the sec.

The authors proved that the B1L isoform is the main regulator of TERT expression in promoter mutated glioblastomas and there is a positive association between TERT and B1L mRNA expression, unlike our correlation results.