Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer:A multicenter retrospective observational comparative study

BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.

Association between Taenia solium infection and HIV/AIDS in northern Tanzania: a matched cross sectional-study

Background:The frequency of Taenia solium,a zoonotic helminth,is increasing in many countries of sub-Saharan Africa,where the prevalence of the human immunodeficiency virus(HIV)is also high.However,little is known about how these two infections interact.The aim of this study was to compare the proportion of HIV positive(+)and negative(−)individuals who are infected with Taenia solium(TSOL)and who present with clinical and neurological manifestations of cysticercosis(CC).Methods:In northern Tanzania,170 HIV+individuals and 170 HIV–controls matched for gender,age and village of origin were recruited.HIV staging and serological tests for TSOL antibodies(Ab)and antigen(Ag)were performed.Neurocysticercosis(NCC)was determined by computed tomography(CT)using standard diagnostic criteria.Neurological manifestations were confirmed by a standard neurological examination.In addition,demographic,clinical and neuroimaging data were collected.Further,CD4^(+)cell counts as well as information on highly active antiretroviral treatment(HAART)were noted.Results:No significant differences between HIV+and HIV–individuals regarding the sero-prevalence of taeniosis-Ab(0.6%vs 1.2%),CC-Ab(2.4%vs 2.4%)and CC-Ag(0.6%vs 0.0%)were detected.A total of six NCC cases(3 HIV+and 3 HIV–)were detected in the group of matched participants.Two individuals(1 HIV+and 1 HIV–)presented with headaches as the main symptom for NCC,and four with asymptomatic NCC.Among the HIV+group,TSOL was not associated with CD4+cell counts,HAART duration or HIV stage.Conclusions:This study found lower prevalence of taeniosis,CC and NCC than had been reported in the region to date.This low level of infection may have resulted in an inability to find cross-sectional associations between HIV status and TSOL infection or NCC.Larger sample sizes will be required in future studies conducted in that area to conclude if HIV influences the way NCC manifests itself.

TFIIA transcriptional activity is controlled by a ＇cleave-and-run＇ Exportin-1/Taspase 1-switc

Transcription factor TFIIA is controlled by complex regulatory networks including proteolysis by the protease Taspase 1, though the full impact of cleavage remains elusive. Here, we demonstrate that in contrast to the general assumption, de novo produced TFIIA is rapidly confined to the cytoplasm via an evolutionary conserved nuclear export signal （NES, amino acids ^21VINDVRDIFL^30）, interacting with the nuclear export receptor Exportin-1/chromosomal region maintenance 1 （Crml）. Chemical export inhibition or genetic inactivation of the NES not only promotes TFIIA＇s nuclear localization but also affects its transcrip- tional activity. Notably, Taspase 1 processing promotes TFIIA＇s nuclear accumulation by NES masking, and modulates its tran- scriptional activity. Moreover, TFIIA complex formation with the TATA box binding protein （TBP） is cooperatively enhanced by inhibition of proteolysis and nuclear export, leading to an increase of the ceil cycle inhibitor p16INK, which is counteracted by pre- vention of TBP binding. We here identified a novel mechanism how proteolysis and nuclear transport cooperatively fine-tune tran- scriptional programs.