色素性乾皮症

Data on the clinical characteristics of keratoacanthomas (KAs) associated with Muir-Torre syndrome (MTS) and xeroderma pigmentosum (XP) are limited. To compare the clinical features of KAs in patients with MTS and XP. Consecutive patients diagnosed with MTS or XP were evaluated for the occurrence of KA in a single dermatology centre. Age at onset, number, size, localization, association with cutaneous horn, and regression patterns of KAs were compared in both groups and with sporadic KAs. A total of 26 KAs were observed in 7 of 38 patients with XP and 11 lesions in 4 of 8 patients with MTS with a mean age at onset of 11.4±6.5 and 50.5±8.5 years, respectively. Most individuals with both syndromes presented with multiple KAs. In MTS patients, lesions involved both facial and truncal sites and were frequently >1 cm in diameter, and spontaneous regression commonly resulted in depressed or hypopigmented, atrophic scars surrounded by a thin rim, and mutilation was observed in one case. In contrast, KAs in XP patients were predominantly localized to the head and neck, with occasional mucosal involvement, and were sometimes associated with cutaneous horn and typically healed with minimal or no scarring. Sporadic KAs manifested mostly as solitary lesions, predominantly on the face, in 14 patients with a mean age of 60.2±14.2 years. KAs in XP and MTS patients differ with regards to age at onset, distribution, associated features, and regression patterns. Truncal involvement, larger size and prominent scarring favour MTS, whereas early onset, mucosal involvement, and association with cutaneous horn are more characteristic of XP.

Lung cancer is one of the most common and deadly forms of cancer worldwide, with >80% of cases being non‑small cell lung cancer. Its recurrence and drug resistance have been major challenges in clinical treatment, posing a serious threat to the lives of patients. The present study found that high xeroderma pigmentosum group C (XPC) expression markedly reduced the proliferation capacity and stem cell characteristics of the lung cancer cell lines A549‑XPC and H460‑XPC. In addition, XPC overexpression led to a decreased in the proportion of cells in the G2/M phase proportion, suggesting alterations in the cell cycle process. MTS assays showed that XPC overexpressing cells demonstrated markedly higher sensitivity to chemotherapy drugs compared with control cells. Furthermore, the clonogenic and anchorage‑independent spheroid formation capacities of the cells were markedly inhibited with high XPC expression and the phosphorylation levels of the JAK/STAT pathway and the expression levels of stemness‑associated markers were markedly altered. In vivo studies validated the effect of high XPC expression on tumorigenicity using a subcutaneous tumor model, with tumor volumes of 134.04±46.77 mm³ and 324.64±85.31 mm³ and weights of 164.24±76.16 mg and 434.70±115.72 mg for subcutaneously injected A549‑XPC and A549‑CTR cells, respectively. High expression of XPC in the A549 cells significantly affected tumor volume (P<0.05) and weight (P<0.01) in vivo. The present findings suggested that high XPC expression is associated with reduced proliferation, migration and stem cell‑like properties in lung cancer cells, enhances their sensitivity to chemotherapy drugs and suppresses tumor growth in vivo. These observations supported further investigation of XPC as a potential therapeutic target and prognostic marker for lung cancer, offering new strategies to improve treatment outcomes and prolong patient survival.

Repair of damaged DNA is a complex process, particularly when it is compacted into nucleosomes. There are a number of genetic disorders with deficiencies in DNA repair. Knowledge of the genes and proteins involved in these repair deficiencies is critical in developing an understanding of the molecular mechanisms utilized by proteins in the DNA repair pathways. One of these genetic disorders is xeroderma pigmentosum (XP), which is defective in nucleotide excision repair (NER). Patients in XP complementation group A (XP-A) are among the most severely affected with the lowest levels of DNA repair. The XPA protein, which is defective in these patients, plays a number of roles in the DNA repair process. One particularly important role proposed is acting as a processivity factor enabling endonucleases (XPF and XPG) and the XPB/TFIIH translocase to localize to damage sites using a processive mechanism of action. Another proposed role is in interacting with chromatin-remodeling proteins so as to enhance accessibility of lesions in nucleosomal DNA to endonucleolytic incision and other DNA repair activities. In XP-A cells, the XPA protein is proposed to be defective in ability to act as a processivity factor; endonucleases localize damage sites by a distributive mechanism and are also defective in incision of damaged nucleosomal DNA. This defect is corrected by recombinant normal human XPA. Mutations in exons 3 and 5 in the DNA binding domain of the XPA gene lead to loss of ability of XPA to act as a processivity factor. The mutation in exon 5 was found in two XP-A patients with severe XP. These studies emphasize the importance of correlating specific mutations in an XP gene and the resulting defect in a particular repair protein with the clinical severity of XP and could lead to development of novel therapeutic approaches for this disorder.