Replication and Virus-Induced Transcriptome of HAdV-5 in Normal Host Cells versus Cancer Cells - Differences of Relevance for Adenoviral Oncolysis

Adenoviruses (Ads), especially HAdV-5, have been genetically equipped with tumor-restricted replication potential to enable applications in oncolytic cancer therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients, but their anti-tumor efficacy needs to be enhanced. In this regard, it should be considered that cancer cells, dependent on their tissue of origin, can differ substantially from the normal host cells to which Ads are adapted by complex virus-host interactions. Consequently, viral replication efficiency, a key determinant of oncolytic activity, might be suboptimal in cancer cells. Therefore, we have analyzed both the replication kinetics of HAdV-5 and the virus-induced transcriptome in human bronchial epithelial cells (HBEC) in comparison to cancer cells. This is the first report on genome-wide expression profiling of Ads in their native host cells. We found that E1A expression and onset of viral genome replication are most rapid in HBEC and considerably delayed in melanoma cells. In squamous cell lung carcinoma cells, we observed intermediate HAdV-5 replication kinetics. Infectious particle production, viral spread and lytic activity of HAdV-5 were attenuated in melanoma cells versus HBEC. Expression profiling at the onset of viral genome replication revealed that HAdV-5 induced the strongest changes in the cellular transcriptome in HBEC, followed by lung cancer and melanoma cells. We identified prominent regulation of genes involved in cell cycle and DNA metabolism, replication and packaging in HBEC, which is in accord with the necessity to induce S phase for viral replication. Strikingly, in melanoma cells HAdV-5 triggered opposing regulation of said genes and, in contrast to lung cancer cells, no weak S phase induction was detected when using the E2F promoter as reporter. Our results provide a rationale for improving oncolytic adenoviruses either by adaptation of viral infection to target tumor cells or by modulating tumor cell functions to better support viral replication

Energy-scaling behavior of intrinsic transverse-momentum parameters in Drell-Yan simulation

Data Availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS data preservation, re-use, and open access policy https://dx.doi.org/10.7483/OPENDATA.CMS.7347.JDWH .A preprint version of the article is available on arXiv, arXiv:2409.17770v2 [hep-ph] (https://arxiv.org/abs/2409.17770). [v2] Tue, 8 Apr 2025 23:23:48 UTC (450 KB). Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/GEN-22-001 (CMS Public Pages). Subjects: High Energy Physics - Phenomenology (hep-ph); High Energy Physics - Experiment (hep-ex). Report numbers: CMS-GEN-22-001, CERN-EP-2024-216An analysis is presented based on models of the intrinsic transverse momentum (intrinsic ) of partons in nucleons by studying the dilepton transverse momentum in Drell-Yan events. Using parameter tuning in event generators and existing data from fixed-target experiments and from hadron colliders, our investigation spans 3 orders of magnitude in center-of-mass energy and 2 orders of magnitude in dilepton invariant mass. The results show an energy-scaling behavior of the intrinsic parameters, independent of the dilepton invariant mass at a given center-of-mass energy.We congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC and thank the technical and administrative staffs at CERN and at other CMS institutes for their contributions to the success of the CMS effort. In addition, we gratefully acknowledge the computing centers and personnel of the Worldwide LHC Computing Grid and other centers for delivering so effectively the computing infrastructure essential to our analyses. Finally, we acknowledge the enduring support for the construction and operation of the LHC, the CMS detector, and the supporting computing infrastructure provided by the following funding agencies: SC (Armenia), BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES and BNSF (Bulgaria); CERN; CAS, MoST, and NSFC (China); MINCIENCIAS (Colombia); MSES and CSF (Croatia); RIF (Cyprus); SENESCYT (Ecuador); ERC PRG, RVTT3 and MoER TK202 (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); SRNSF (Georgia); BMBF, DFG, and HGF (Germany); GSRI (Greece); NKFIH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); MES (Latvia); LMTLT (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MOS (Montenegro); MBIE (New Zealand); PAEC (Pakistan); MES and NSC (Poland); FCT (Portugal); MESTD (Serbia); MCIN/AEI and PCTI (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); MHESI and NSTDA (Thailand); TUBITAK and TENMAK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA)

Treatment Outcome and Skin Complications in Tumor Bed Boost Radiotherapy Using Photons or Electrons in Breast Cancer Patients after Breast-Conserving Surgery

Background and Objective: In patients with breast cancer, the administration of an additional dose of radiotherapy to the tumor bed after breast treatment is associated with a decrease in local recurrence. Electron source is mainly used due to proper dose distribution and lack of skin irradiation. Nevertheless, access to electrons is not possible in all medical centers. Therefore, continuing treatment using smaller photon fields may be a reasonable option. The aim of this study is to investigate and compare the outcome of treatment and skin complications in tumor bed boost radiotherapy using photons or electrons in breast cancer patients after breast-conserving surgery. Methods: In this retrospective cohort, 280 patients with non-metastatic breast cancer who underwent breast-conserving surgery and adjuvant radiotherapy were included in the study. After whole breast radiotherapy with conventional regimen (50 Gy in 25 sessions), the patients underwent tumor bed boost with electrons or photons (with a dose of 10 Gy in 5 sessions) (electron: 145 people, photon: 135 people). Survival values, cosmetic results (Harvard Harris criteria) and skin toxicity (5th edition of General Toxicity Criteria and Adverse Effects) were compared between the two groups during the follow-up of patients. Findings: Recurrence-free survival in the same breast was not significantly different in two groups (recurrence-free survival in photon boost 95% (with a 95% confidence interval between 9% and 97%) and electron boost 93% (with a 95% confidence interval between 79% and 97) (p=0.69). There was no difference between radiotherapy-induced dermatitis and subcutaneous toxicity at the end of the treatment between the two treatment groups. However, one month after the end of the treatment, the cases of severe radiotherapy-induced dermatitis were higher in the photon treatment group (88% vs. 65.5%, p=0.007). However, the subcutaneous toxicity 2 months after the end of treatment was significantly higher in the electron boost group (0% vs. 7.5%, p<0.05). Mild pain in the same breast 6 months after the end of the treatment was higher in the photon treatment group (0% vs. 8.9%, p<0.001). Conclusion: Based on the results of the present study, using an electron or photon source to boost the dose to the tumor bed following whole breast radiotherapy in breast cancer patients undergoing breast-conserving surgery is associated with similar treatment results in terms of recurrence in the same breast. Of course, the toxicity profile, especially the skin toxicity, is different between the two approaches