Molecular and clinical oncology最新文献

Breast cancer is the most common cause of cancer worldwide and is the leading cause of mortality for women across most of the world. Immunotherapy is a burgeoning area of cancer treatment, including for breast cancer; these are therapies that harness the power of the immune system to clear cancerous cells. Toll-like receptor 3 (TLR3) is an RNA receptor found in the endosome, and ligands that bind to TLR3 are currently being tested for their efficacy as breast cancer immunotherapeutics. The current review introduces TLR3 and the role of this receptor in breast cancer, and summarizes data on the potential use of TLR3 ligands, mainly polyinosinic:polycytidylic acid and its derivatives, as breast cancer monotherapies or, more commonly, as combination therapies with chemotherapies, other immunotherapies and cancer vaccines. The current state of TLR3 ligand breast cancer therapy research is summarized by reporting on past and current clinical trials, and notable preliminary in vitro studies are discussed. In conclusion, TLR3 ligands have robust potential in anticancer applications as innate immune stimulants, and further studies combined with innovative technologies, such as nanoparticles, may contribute to their success.

Telomeres are tandem repeats of DNA sequences protecting the end of linear chromosomes. Replicative senescence due to telomere attrition is considered a tumor-preventing mechanism in differentiated somatic cells. However, telomere shortening is associated with genome instability and several disease entities. During carcinogenesis, the development of a telomere maintenance mechanism, predominately through the activation of the telomerase enzyme, represents a hallmark of cancer, since it enables cancer cells to avert senescence and divide indefinitely. Although research of the involvement of telomeres and telomerase in various malignant neoplasms has gained a large amount of interest, the timing and relevance of their role in pre-neoplastic lesions remain to be determined. The present narrative review aims to summarize the evidence regarding the role of telomeres and telomerase in pre-neoplasia across different types of tissues.

Myelodysplastic/myeloproliferative neoplasm with neutrophilia (MDS/MPN-N; previously referred to as atypical chronic myeloid leukemia) is a type of myelodysplastic syndrome/myeloproliferative neoplasm. A molecular genetic precondition for diagnosis is BCR::ABL negativity; further diagnostic criteria include clinicopathological assessments, such as peripheral blood leukocyte counts, the number of neutrophils and their precursors, and the presence of dysgranulopoiesis. The present case report highlights the importance of differential diagnoses with a stringent diagnostic workup according to the 5th Edition of the World Health Organization Classification of Hematolymphoid Tumors. A systematic review of the literature from 2013 to 2022 covering the mutational landscape of MDS/MPN-N was also performed to highlight recent improvements in the molecular genetic diagnostics of this disease.

Lung squamous cell carcinoma (LSCC) is associated with poor prognosis. Molecular targeting drugs have been demonstrated to be effective for lung adenocarcinoma; however, they are often not effective for LSCC. Kallikrein-related peptidase 13 (KLK13) expression enhances the malignancy of lung adenocarcinoma; however, its expression and crucial role in LSCC remain largely unknown. The present study examined the relationship between the KLK13 expression and clinicopathological features of LSCC. A total of 94 patients diagnosed with LSCC who underwent lobectomy, segmentectomy or wedge resection were selected. KLK13 expression was evaluated through immunostaining of formalin-fixed paraffin-embedded sections of surgical specimens. Of the 94 LSCC samples, 70 exhibited no KLK13 expression, while the remaining 24 exhibited ectopic expression. KLK13 expression in tumors was focal and restricted to the cytoplasm of keratinized cells. LSCC cases were classified into KLK13-negative and KLK13-positive groups, and KLK13 expression was positively associated with E-cadherin expression (P=0.0143). Associations between KLK13 expression and keratinization (P=0.0052) or absence of lymphatic vessel invasion (P=0.0603) were observed; however, these trends did not reach statistical significance. The present findings indicated that KLK13 expression in keratinized LSCC may have a protective role in lymphatic vessel invasion of LSCC, which suggests its significance for therapeutic applications against LSCC.

Trastuzumab and pertuzumab with taxane-based chemotherapy are considered the first-line standard therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). Pertuzumab is also a later-line therapy for mBC in Switzerland, although limited safety and efficacy data are available. The present study assessed the therapeutic regimens, toxicities and clinical outcomes after second- or later-line pertuzumab therapy in patients with mBC who did not receive pertuzumab as a first-line therapy. Physicians from nine major Swiss oncology centers retrospectively completed a questionnaire for each pertuzumab-naive patient who was treated with pertuzumab as a second- or later-line therapy. Of 35 patients with HER2-positive mBC (median age, 49 years; range, 35-87 years), 14 received pertuzumab as a second-line therapy, 6 as a third-line therapy, and 15 as a fourth- or later-line therapy. A total of 20 patients (57%) died during the study period. The median overall survival was 74.2 months (95% confidence interval, 47.6-139.8 months). Grade (G) 3/4 adverse events (AEs) were reported in 14% of patients, with only 1 patient discontinuing therapy due to pertuzumab-related toxicities. The most common AE was fatigue (overall, 46%; G3, 11%). Overall, congestive heart disease occurred in 14% of patients (G3, 6%), nausea in 14% of patients (all G1), and myelosuppression in 12% of patients (G3, 6%). In conclusion, the median overall survival of patients who underwent second- or later-line pertuzumab treatment was similar to that reported for patients who underwent first-line pertuzumab treatment, and the safety profile was acceptable. These data support the use of pertuzumab for second- or later-line therapy when it was not administered as first-line therapy.

Post-mastectomy radiotherapy (PMRT) is highly recommended for patients with breast cancer with one to three positive nodes; however, there remains some controversy regarding its use. The present retrospective study aimed to explore which patients may be able to avoid PMRT and its associated side effects. A total of 728 patients with T1-2N1 breast cancer who were treated with or without PMRT were included in the present study. The results suggested that PMRT significantly decreased the locoregional recurrence rate (LRR) [hazard ratio (HR)=5.602, 95% confidence interval (CI)=3.139-9.998, P<0.01; 3-year LRR: 4 vs. 17%] and improved overall survival (OS) (HR=0.651, 95% CI=0.437-0.971, P=0.03; 3-year OS: 91 vs. 87%) for patients with T1-2N1 breast cancer. By contrast, PMRT had no significant effect on the distant metastasis (DM) rate (HR=0.691, 95% CI=0.468-1.019, P=0.06; 3-year DM: 10 vs. 15%). Further stratified analysis revealed that PMRT did not reduce the LRR and DM, or improve OS in patients aged ≤35 years or in those with a positive human epidermal growth factor receptor-2 (HER-2) status. The analysis of 438 patients treated with PMRT revealed that patients aged ≤35 years or those with a positive HER-2 status were more likely to experience local recurrence even following PMRT. Thus, the benefits of using PMRT in patients with T1-2N1 breast cancer who are aged ≤35 years or in those with a positive HER-2 status need to be carefully considered. Further studies are required to confirm whether this patient group may be exempted from PMRT.

Patients with recurrent cervical cancer have limited treatment options and are often considered to be incurable. Since the expression of amphoterin-induced gene and open reading frame 2 (AMIGO2) in clinical samples is a prognostic factor for colorectal cancer and gastric cancer, the present aimed to elucidate whether it is also a prognostic factor for cervical cancer. Patients with primary cervical cancer who underwent radical hysterectomy or radical trachelectomy at our institution (Faculty of Medicine, Tottori University, Yonago, Japan) between September 2005 and October 2016 were retrospectively collected. Immunohistochemical analysis using a specific antibody against AMIGO2 was performed on 101 tumor samples, and the clinical characteristics, disease-free survival (DFS) and overall survival (OS) of the patients were examined. Patients in the AMIGO2-high group had a shorter 5-year DFS and OS than those in the AMIGO2-low group (P<0.001). Furthermore, AMIGO2 was an independent prognostic factor for DFS in multivariate analysis (P=0.0012). Patients in the AMIGO2-high group exhibited obvious recurrence compared with those in the AMIGO2-low group in the high-(P=0.03) and intermediate-risk groups (P=0.003). Positive lymph node metastasis, and parametrial, stromal and lymph vascular space invasion were significantly more common in AMIGO2-high patients. Taken together, AMIGO2 expression may be a predictive marker of recurrence for cervical cancer. In particular, it may be an indicator to determine the need for postoperative adjuvant therapy in intermediate-risk group patients.

The present study aimed to determine the expression levels of p53 in patients with hepatocellular carcinoma (HCC) and to evaluate its association with several HCC-related prognostic factors and in particular, with tumor stage, grade and subtype. Therefore, a cross-sectional study, involving 41 patients with HCC, who underwent surgical resection between January, 2013 and December, 2020 was conducted. To assess the expression levels of p53 in all patients with HCC, immunohistochemical staining was performed. In addition, the association between p53 expression and the clinicopathological characteristics of patients with HCC, including prognostic factors, was evaluated by applying the appropriate statistical analysis methods. The results revealed that among the 41 patients enrolled, 35 patients (85.4%) were positive for p53 expression. A higher percentage of positive p53 expression was observed in male patients >60 years old, with single HCC nodules >5 cm in diameter and vascular invasion, compared with their counterparts. A positive p53 expression was associated with well- and poorly differentiated HCC, but not with tumor stage and subtype. No differences in p53 expression were observed across different tumor stages and subtypes. Additionally, patients with moderately and poorly differentiated HCC exhibited significantly higher p53 expression levels compared with those suffering from well-differentiated HCC. Overall, the results demonstrated that the rate of p53 immuno-positive cells was increased in patients with HCC. In addition, p53 expression was associated with well- and poorly differentiated HCC, thus suggesting its association with a poorer prognosis.

Few large population-based studies have examined the prevalence of atrophic gastritis (AG) and Helicobacter pylori infection in Japan. The purpose of the present study was to estimate the prevalence of AG and H. pylori infection by age, in addition to investigating their change rates from 2005 to 2016 in Japan using data from a large population-based cohort. A total of 3,596 participants [1,690 in the baseline survey (2005-2006) and 1,906 at the fourth survey (2015-2016)] aged 18 to 97 years were included in the cohort. The prevalence of AG and H. pylori infection were examined at baseline and in the fourth survey based on serological tests for the H. pylori antibody titer and pepsinogen levels. The prevalence of AG and H. pylori infection were 40.1% (men, 44.1%; women, 38.0%) and 52.2% (men, 54.8%; women, 50.8%), respectively, at baseline. AG seropositivity rates showed a significant decrease from 40.1 to 25.8% in 10 years. H. pylori seropositivity rates decreased significantly from 52.2 to 35.5% in 10 years. Stratified for age, the prevalence of AG showed an increasing trend with age, whereas the prevalence of H. pylori infection increased with aging, except for in the elderly group, showing an inverted U-shaped association. In this population-based, cross-sectional study with a 10-year interval survey, the prevalence of AG and H. pylori infection decreased significantly. This change may influence the prevalence of H. pylori-related diseases, including extra-gastric disorders associated with H. pylori-induced systemic subclinical inflammation and hypochlorhydria, such as colorectal neoplasia and arteriosclerosis.

Endometrial cancer is the fifth most common female cancer worldwide and the third leading female cancer in the Western world. The marked surge in endometrial cancer incidence is alarming. The aim of the present review is to focus on endometrial cancer affecting young women of reproductive age. Surgery, namely abdominal or laparoscopic hysterectomy, with or without salpingo-oophorectomy, and sentinel lymph node detection has become the standard surgical strategy for early stage endometrioid endometrial cancer. However, premenopausal women might want to preserve their fertility, especially if they are nulliparous or have not reached their desired number of children at the time of diagnosis. Conservative, uterus-sparing treatment, based on progestin products, may be an advantageous option for patients meeting the necessary criteria. Potential candidates have to be committed to following a rigorous protocol of treatment, investigations and follow-up. The evidence in favor of this approach, although limited, is encouraging and patients who have achieved a histologically documented disease complete remission could attempt to conceive spontaneously or with the immediate use of assisted reproductive technology techniques. The risk of partial or negative response to progestin treatment or cancer recurrence is well documented, thus patients have to be aware of the possible need for interruption of conservative treatment and hysterectomy.