International Journal of Cancer最新文献

As a tumor suppressor gene, CCDC6 encodes a coiled-coil domain-containing protein that is ubiquitously expressed and involved in crucial cellular processes such as DNA damage response and apoptosis, although its precise mechanisms remain elusive. Initially identified as part of a fusion gene, CCDC6 can form fusion genes with a variety of proto-oncogenes, including both kinase- and non-kinase-coding genes, thereby facilitating oncogenesis. Alterations in CCDC6 expression across various cancers underscore its intricate role and potential influence on the efficacy of anticancer therapies. Recent findings have demonstrated that CCDC6 can undergo liquid-liquid phase separation (LLPS) and facilitate the LLPS of its associated fusion proteins, providing new perspectives on its functional characterization and potential therapeutic implications in related diseases. We present a comprehensive overview of CCDC6, encompassing its protein characteristics and physiological and genomic aspects. Furthermore, we explored the association between CCDC6 alterations and carcinogenesis, as well as their implications for therapeutic interventions. The objective of this review is to furnish the medicinal community with current information and valuable insights pertaining to diseases associated with CCDC6.

CAR-T cell therapy is a representative form of adoptive cancer immunotherapy. This review summarizes recent advances in CAR-T cell therapy and associated laboratory tests for clinical practice. CAR-T cell therapy is designed to enhance T cell immunity, distinguishing it from conventional cancer treatments such as surgery, chemotherapy, or radiotherapy. It has shown significant efficacy in hematologic malignancies but continues to yield limited results in many solid tumors. Intensive research efforts are underway to develop more potent CAR-T cells and to uncover mechanisms of resistance. For broader clinical application, the development of reliable biomarkers and standardized management guidelines is essential. These include criteria for evaluating leukapheresis success, tests for CAR-T efficacy, biomarkers for prognosis or resistance, and laboratory assays for detecting side effects and toxicity. Recent progress in laboratory diagnostics in the clinical field will play a pivotal role in optimizing patient management in the era of CAR-T cell therapy.

Cervical cancer (CC) mortality in the Baltic countries remains high. We explored CC mortality trends and educational inequalities in CC mortality in the Baltics in the context of organized CC screening (introduced in 2004 in Lithuania, 2006 in Estonia and 2009 in Latvia) and compared the results with Finland (where screening started in 1963). Data for the Baltic countries came from longitudinal mortality follow-up studies of population censuses in 2000/2001 and 2011, and data for Finland from the longitudinal register-based population data file of Statistics Finland. CC deaths (ICD-10 code C53) were linked from national mortality registries. Information on education was census- or register-based. Overall and education-specific age-standardized mortality rates (ASMRs) and mortality rate ratios were calculated for 2000-2007 and 2008-2015 for women aged 30-49 and 50-64 years. The Baltic countries had 5-9 times higher overall ASMRs than Finland and much larger inequalities in CC mortality between low- and highly educated women. From 2000-2007 to 2008-2015 absolute inequalities in younger women reduced in all countries, except Latvia and relative inequalities increased in Estonia and Latvia. In older women, absolute inequalities increased in the Baltics but not in Finland; relative inequalities increased in all countries. The reduction in CC mortality and in absolute inequalities in younger women in Estonia and Lithuania may be associated with the introduction of organized screening. However, increasing CC mortality among older low-educated women in the Baltic countries is alarming, indicating that they have not benefitted equally from CC prevention.

There is little information on non-thyroid cancer risks, including haematological malignancies (HM), among the residents of most contaminated regions after the Chernobyl (Chornobyl) nuclear power plant accident. We studied the incidence of lymphoma, multiple myeloma and leukaemia in relation to the raion-average age-specific cumulative absorbed red bone marrow (RBM) dose among the residents of Gomel and Mogilev oblasts in Belarus, which were highly contaminated. The follow-up period was 40 years (1978-2018). HM cases and population size data were received from the Belarusian national cancer registry and the state department of statistics. Our ecological study included 7328 lymphoma, 9476 leukaemia and 2003 multiple myeloma incident cases and 90.8 million person-years in people who were born before the accident and have attained age <80 years old. The mean (median) RBM dose accumulated by December 31, 2018 was 14.2 (6.4) mGy. We found no evidence of increased risks of Hodgkin and non-Hodgkin lymphoma, multiple myeloma or total leukaemia associated with two-year lagged raion-average cumulative RBM dose after adjustment for sex, attained age, urban/rural status and calendar period effects. There was a suggestion of an elevated relative risk of myeloid leukaemia per 100 mGy after exclusion of Gomel and Mogilev cities. Little evidence was found on interaction between selected factors, except sex, and RBM dose for each study outcome. Studies with individually reconstructed cumulative absorbed RBM doses are warranted to provide more insight on dose-effect relationships between HM risk, specifically leukaemia, and protracted environmental exposure at a low dose range.

Gastric carcinoma (GC) with neuroendocrine differentiation (GCNED) is a rare and particular pathological subtype. The survival outcomes and prognosis of patients with GCNED are currently unclear. We conducted a retrospective cohort study including 309 patients with GC diagnosed between 2012 and 2024 to clarify outcomes after radical resections. Neuroendocrine differentiation was identified using immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule expression. The results showed a GCNED-positivity rate of 22.3% (69/309). The only significant difference in clinicopathological characteristics was the higher perineural invasion (PNI) rate in patients with GCNED-positivity (29% vs. 15.8%, p = .014). Factors such as age, sex, TNM stage, and lymphovascular invasion showed no differences. Regardless of the GCNED-positivity cutoff value (1%, 10%, or 20%), no statistically significant differences in overall survival (OS) or recurrence-free survival (RFS) rates were observed between the two groups. However, in the differentiated histology group, patients with GCNED-positivity showed worse survival rates (p = .015). Logistic regression identified PNI as an independent risk factor for GCNED positivity (odds ratio, 2.08; 95% confidence interval, 1.11-3.91; p = .022). The study showed that while GCNED has a non-negligible prevalence, it has no significant effect on OS or RFS outcomes for patients after radical resections compared to GC without neuroendocrine features. The trend toward a worse prognosis in specific subgroups, such as patients with differentiated GCNED, suggests biological heterogeneity and warrants a longer follow-up to inform stratified therapies.

During the first year of the COVID-19 pandemic, reported cancer cases declined in the Nordic countries, potentially reflecting delays in cancer diagnosis. We compared 1-year relative survival (RS) and excess mortality of patients diagnosed with cancer in the Nordic countries in March-December 2020 with that expected based on patients diagnosed in 2011-2019. We used flexible parametric RS models, defining excess mortality as the difference in total mortality between patients with cancer and the national population without cancer. We report the ratio between the observed and expected excess mortality (EMR) and the difference in 1-year RS in percentage points (pp) by country, age, sex, and cancer site. Excess mortality of patients diagnosed during the pandemic was increased in all Nordic countries except Iceland. Swedish men had the highest EMR of 1.12 (95% CI 1.06, 1.17), corresponding to a 1.4 pp reduction in 1-year RS (87.1%-85.8%). In women, the highest EMR was 1.10 (95% CI 1.03, 1.18) in Norway, corresponding to a 1-year RS decrease of 1.2 pp (86.6%-85.5%). The largest site-specific decreases in 1-year RS were observed for liver cancer in Finnish and Swedish men, with decreases of 10.2 pp (45.3%-35.1%) and 7.2 pp (55.7%-48.5%), respectively. We found reduced 1-year RS among Nordic patients diagnosed with cancer during the COVID-19 pandemic in 2020, especially in older patients and those with aggressive cancers. These reductions coincided with restrictions and potential delays in seeking healthcare.

Cancer patients have an increased risk of thromboembolic events. Consequently, anticoagulants such as rivaroxaban are often prescribed. With the increasing use of targeted therapies, there is a growing concern about potential drug-drug interactions, as these therapies can affect metabolic enzymes and transporters (i.e., cytochrome P450 3A and P-glycoprotein). When used in combination with rivaroxaban, these interactions may elevate a patient's risk of thromboembolic events or bleeding. Our primary objective was to investigate the effect of sotorasib on the pharmacokinetics of rivaroxaban and determine the safety of this combination in healthy volunteers. In an open label, single-sequence, pharmacokinetic drug-drug interaction study in healthy subjects, the influence of a once-daily 960 mg dose sotorasib for a period of 14 days was evaluated on the pharmacokinetics of a single 20 mg dose rivaroxaban. This clinical study followed the FDA guidance on drug interaction studies. A clinically relevant pharmacokinetic interaction was considered absent if the 90% confidence intervals (CIs) of the geometric mean ratios for C_max and AUC_0-∞ were within the no-effect boundaries of 0.70-1.43. A total of 20 healthy subjects completed the study. The geometric mean ratios 1.00 (90% CI 0.90-1.12) for C_max and 0.79 (90% CI 0.73-0.86) for AUC_0-∞ fell inside the predefined criteria, indicating no clinically relevant pharmacokinetic interaction. In addition, rivaroxaban and sotorasib were well tolerated by the healthy subjects. These results suggest that rivaroxaban can be safely co-administered without the need for switching to another treatment or dose adjustments in patients treated with sotorasib.

Prophylactic vaccination is a powerful tool that changes exposure to infections and associated morbidity of preventable diseases. We discuss the impact of pneumococci and human papillomavirus (HPV) vaccination on the population biology of the two micro-organisms and related public health effects. Data on HPV type-replacement in communities where vaccine-covered HPVs are almost eliminated, and interactions of the remaining HPV types on the risk of cervical cancer are reviewed. Results of comprehensive models for European country-specific conduction of cervical screening among HPV-vaccinated and unvaccinated women, assuming different HPV-vaccination coverage and strategies, are discussed in our policy-oriented review. An acceptable balance of benefits and harms of cervical cancer screening in HPV vaccinated populations requires an understanding of cancer risks in differently vaccinated birth cohorts. Finally, the challenges are complex but can be met if strategies are applied that (i) as fast as possible achieve herd effect and (ii) use a risk-based design of HPV screening.

Low triiodothyronine (T3) syndrome, also known as non-thyroidal illness syndrome (NTIS), was one of the common endocrinopathies in critical illness. The potential impacts of low T3 syndrome on survival, endocrine function, and nutritional status of patients with aggressive mature B-cell non-Hodgkin lymphoma (NHL) needed to be explored. We enrolled 225 patients. T3 levels were captured when starting chemotherapy, finishing chemotherapy, and at the first follow-up visit from 6 months after chemotherapy. Latest ultrasound results were recorded. Kaplan-Meier curves were used to compare overall survival (OS) or progression-free survival (PFS). We performed Cox's proportional hazards regression model to analyze prognostic factors of OS and PFS. Ultrasound abnormality and weight gain were tested with the χ² test. The percentage of patients with low T3 syndrome decreased from 55.1% (124 out of 225) to 2.0% (4 out of 201), then further dropped down to 0 (0 out of 173). With a median follow-up of 32.9 months, low T3 syndrome was identified as a statistically significant factor affecting both OS (p = .047; hazard ratio [HR] = 8.18, 95% CI: 1.03-64.97) and PFS (p = .049; HR = 4.64, 95% CI: 1.01-21.31) in multivariate analysis. No significant effects of low T3 syndrome on abnormal thyroid ultrasound results and weight gain were found. In conclusion, low T3 syndrome has a high incidence in pediatric patients with aggressive mature B-cell NHL, and low T3 syndrome has a significant impact on long-term survival. It appears transient and could not contribute to impaired thyroid function.

As cervical cancer screening shifts from cytology to HPV testing, clarifying the type- and age-specific natural history of HR-HPV is crucial, especially in regions with bimodal prevalence patterns where longitudinal data remain limited. We analyzed baseline HR-HPV-positive participants from the control arm of a bivalent HPV-16/18 vaccine trial in China, with follow-up over 5.5 years. Cox regression and competing risk models were applied to evaluate the progression, clearance, and persistence of these HR-HPV infections. Among 534 HR-HPV-positive women at baseline, 98 CIN2+ lesions were identified (52 at baseline, 46 during follow-up). HPV-16 and HPV-31 exhibited the highest immediate CIN2+ risk (21.1%), followed by HPV-33 (17.1%) and HPV-58 (12.7%). When stratified by baseline cytology, the LSIL+ group showed the highest immediate risk of CIN2+ (29.5% among the HR-HPV-positive participants), followed by the ASC-US (10.5%). In the longitudinal analysis, competing risk models revealed significant type-specific differences in progression (Gray's test P = 0.0158) and clearance (Gray's test P <0.0001). HPV-16, -31, -18, and -58 showed relatively high progression (27.1%, 19.2%, 16.1%, and 11.2%) and low clearance (72.9%, 69.2%, 83.9%, and 88.8%). CIN2+ risk was strongly genotype-dependent; beyond HPV-16/18, types -31, -33, and -58 also warrant particular attention in screening and clinical management. Additionally, although a slightly higher CIN2+ progression risk was observed in younger women compared to older women, the difference was not statistically significant (Gray's test P = 0.4389), indicating the need for confirmation in larger studies. These findings enhance the understanding of the natural history of type-specific HR-HPV and age-specific progression in initially screen-positive populations.