Pathologie (Heidelberg, Germany)最新文献

Background: In 2020, the Organised Early Cancer Diagnosis Guideline (eKFE-RL) programme was introduced in Germany. Women up to the age of 34 years are entitled to annual cytology-based screening. Women aged 35 years and over are entitled to a combined test (cytology and HPV) every 3 years. An age-related assessment algorithm determines the procedure if there are abnormal findings.

Method: A total of 222,851 data were evaluated and analysed from the first round of screening in 2020-2021 according to the oKFE-RL: the prevalence of HPV, its age distribution in general and in HPV-positive findings (n = 10,405), as well as the distribution of HPV 16, 18 and other HPV types, are shown in cervical intraepithelial neoplasia (CIN) lesions. CIN 3 lesions are depicted and compared with the baseline value for 2019.

Results: A threefold increase in CIN 3 compared with 2019 was determined. The peak age for CIN 3 is in women aged 35-39 years. The HPV-positive rate is 8.11 %.

Background: Although autopsy techniques have remained virtually unchanged for almost 150 years, the scientific potential of biomaterials and data from autopsies has evolved significantly due to advances in analytical methods, imaging techniques, and computer-assisted analysis.

Materials and methods: Native and contrast-enhanced postmortem imaging techniques were established and evaluated in clinical autopsies. Contrast-enhanced postmortem imaging was used as a translational tool to quantify renal vascular density in chronic kidney disease. The value of biomaterials from clinical autopsies for translational research was investigated. The establishment of a national autopsy registry enabled comprehensive analyses of data obtained from autopsies.

Results: The development, application, and evaluation of native and contrast-enhanced postmortem imaging techniques; the translational use of postmortem imaging; and the application of various molecular biological methods to biomaterials obtained from autopsies, as well as the collection and systematic analysis of data from autopsies, each showed unique potential. This is not only applicable to further development of postmortem diagnostics, but also to translational research.

Conclusions: Postmortem biomaterials and data are unique for many scientific questions, for example in multisystem diseases and complex disease progression. It is therefore crucial that we, as a pathology community, use and further develop innovative methods in the field of autopsy.

Background: Muscle-invasive bladder cancer (MIBC) includes histological subtypes such as urothelial carcinoma (UC) and the rarer, prognostically unfavorable, squamous cell carcinoma (SCC). Standard treatment is radical cystectomy, while alternatives like chemotherapy or radiotherapy are particularly limited in SCC. Radiosensitizers, such as DNA-dependent protein kinase (DNA-PK) and DNA polymerase theta (POLQ) inhibitors, could selectively enhance radiotherapy effects in tumor cells and represent promising approaches for clinical translation.

Objective: This study analyzed the radiosensitizing effects of DNA-PK and POLQ inhibition ex vivo in patient-derived MIBC cell lines of UC and SCC subtypes.

Materials and methods: The DNA-PK inhibitor AZD7648 (DNA-PKi) and the POLQ inhibitor ART558 (POLQi) were tested ex vivo in patient-derived SCC (p-SCC; n = 3) and UC (p-UC; n = 3) cell cultures. Effects were assessed in combination with ionizing radiation (IR) using XTT cell viability assays (IC50), clonogenic survival assays, γH2AX immunofluorescence, and comet assays.

Results: DNA-PKi strongly radiosensitized MIBC cultures ex vivo, reducing IC50-XTT values by 74-99% and survival rates by 34-64%. Under POLQi +2 Gy, IC50 decreased by 7-13%, whereas under POLQi +8 Gy it increased by 11-24%, with only ~5% reduction in survival. DNA-PKi markedly delayed DNA repair (comet tail moments 38-40%, γH2AX foci increased 11.9-13.1-fold), while POLQi showed minimal effects (comet tail moments 22-33%, γH2AX foci increased 5.4-6.0-fold).

Conclusion: DNA-PKi radiosensitized MIBC cells more effectively than POLQi, particularly SCC. DNA damage response (DDR) inhibitors thus have therapeutic potential in MIBC, depending on the target protein and tumor subtype.