Cancers

Introduction: Small bowel cancer is very rare; although the incidence of adenocarcinoma and other anatomopathological forms has increased recently, the diagnosis and treatment of this disease are still debatable because of the clinical heterogeneity and the absence of studies including a large number of patients. Materials and Methods: We performed a retrospective study over 10 years in which we analyzed the clinical, imaging, and anatomopathological data of 46 patients hospitalized in a surgery clinic and diagnosed with small bowel cancer (duodenum, jejunum, and ileum). Results: After clinical assessment of these patients, including complications (occlusion, bleeding, and perforation), the CT scan established the diagnosis in over 90% of the cases of the complicated form of the disease. Surgery has a curative role in localized cancers; tumor location, local invasion, the presence of locoregional lymph nodes, and the number of multiple tumors influence the type of surgery. The conventional pathological exam was completed via immunohistochemical staining. Adjuvant oncological treatment was performed after surgery (according to the guidelines); in patients with exceptional histopathological forms, the therapy was personalized. Conclusions: Most small bowel cancers were diagnosed with complications (occlusion and bleeding); the tumor type, location, and presence of multiple bowel cancers significantly influenced its management. Independently of the surgical resection (R0/R1 or R2), the prognosis of the disease depends on the tumor aggressivity, location (single/multiple), and locoregional node invasion.

Background: Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. Methods: Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. Results: CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. Conclusions: Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy.

Background: While miRNAs are increasingly recognized for their role in tumorigenesis, their involvement in head and neck cancer (HNC) remains insufficiently explored. Additionally, the carcinogenic mechanisms of areca nut, a major habitual carcinogen in Southeast Asia, are not well understood. Methods and results: This study adopts a systematic approach to identify miRNA profiles associated with areca nut-induced HNC. Using miRNA microarray analysis, we identified 292 miRNAs dysregulated in areca nut-treated HNC cells, with 136 upregulated and 156 downregulated. Bioinformatic analysis of the TCGA-HNSC dataset uncovered a set of 692 miRNAs relevant to HNC development, comprising 449 overexpressed and 243 underexpressed in tumor tissues. Integrating these datasets, we defined a signature of 84 miRNAs, including 39 oncogenic miRNAs (OncomiRs) and 45 tumor-suppressive miRNAs (TsmiRs), highlighting their pivotal role in areca nut-induced carcinogenesis. MultiMiR analysis identified 740 genes cross-regulated by eight hub TsmiRs, significantly impacting key cancer-related pathways (p53, PI3K-AKT, MAPK, and Ras) and critical oncogenic processes. Moreover, we validated miR-499a-5p as a vital regulator, demonstrating its ability to mitigate areca nut-induced cancer progression by reducing cell migration, invasion, and chemoresistance. Conclusions: Thus, this miRNA signature addresses a crucial gap in understanding the molecular underpinnings of areca nut-induced carcinogenesis and offers a promising platform for clinical applications in risk assessment, diagnosis, and prognosis of areca nut-associated malignancies.

Background: Daratumumab (Dara) is the first monoclonal antibody introduced into clinical practice to treat multiple myeloma (MM). It currently forms the backbone of therapy regimens in both newly diagnosed (ND) and relapsed/refractory (RR) patients. However, previous reports indicated an increased risk of infectious complications (ICs) during Dara-based treatment. In this study, we aimed to determine the profile of ICs in MM patients treated with Dara-based regimens and establish predictors of their occurrence. Methods: This retrospective, real-life study included MM patients treated with Dara-based regimens between July 2019 and March 2024 at our institution. Infectious events were evaluated using the Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The study group consisted of a total of 139 patients, including 49 NDMM and 90 RRMM. In the RR setting, the majority (60.0%) of patients received the Dara, bortezomib, and dexamethasone (DVd) regimen, whereas ND patients were predominantly (98%) treated with the Dara, bortezomib, thalidomide, and dexamethasone (DVTd) regimen. Overall, 55 patients (39.6%) experienced ICs. The most common IC was pneumonia (37.5%), followed by upper respiratory tract infections (26.8%). Finally, twenty-five patients had severe ICs (grade ≥ 3) and required hospitalization, and eight patients died due to ICs. In the final multivariable model adjusted for setting (ND/RR) and age, hemoglobin level (OR 0.77, 95% CI: 0.61–0.96, p = 0.0037), and Eastern Cooperative Oncology Group (ECOG) >1 (OR 4.46, 95% CI: 1.63–12.26, p = 0.0037) were significant factors influencing severe IC occurrence. Additionally, we developed predictive models using the J48 decision tree, gradient boosting, and random forest algorithms. After conducting 10-fold cross-validation, these models demonstrated strong performance in predicting the occurrence of pneumonia during treatment with daratumumab-based regimens. Conclusions: Simple clinical and laboratory assessments, including hemoglobin level and ECOG scale, can be valuable in identifying patients vulnerable to infections during Dara-based regimens, facilitating personalized prophylactic strategies.

Introduction: Radiotherapy is an effective method of treating cancer and affects 50% of patients. Intensity-modulated radiotherapy (IMRT) is a modernized method of classical radiation used in the treatment of laryngeal cancer. Treatment with intent to preserve the larynx is not always safe or complication-free. The microbiome may significantly influence the effectiveness of oncological treatment, especially radiotherapy, and may also be modified by the toxic response to radiation. Objective: The aim of the study was to prospectively assess the microbiome and its influence on radiotherapy toxicity in patients with laryngeal cancer. Results: Statistically significant risk factors for complications after radiotherapy were the percentage of Porphyromonas of at least 6.7%, the percentage of Fusobacterium of at least 2.6% and the percentage of Catonella of at least 2.6%. Conclusions: The importance of the microbiome in oncology has been confirmed in many studies. Effective radiotherapy treatment and the prevention of radiation-induced oral mucositis is a challenge in oncology. The microbiome may be an important part of personalized cancer treatment. The assessment of the microbiome of patients diagnosed with cancer may provide the opportunity to predict the response to treatment and its effectiveness. The influence of the microbiome may be important in predicting the risk group for radiotherapy treatment failure. The possibility of modifying the microbiome may become a goal to improve the prognosis of patients with laryngeal cancer. Fusobacterium, Porphyromonas and Catonella are important risk factors for radiation-induced oral mucositis in patients with laryngeal cancer.

Background and Objective: The role of urine cytology during follow-up for low-grade (LG) non-muscle-invasive bladder cancer (NMIBC) is not well established, although cytology has low sensitivity in detecting LG recurrences. Our study aims to evaluate the impact of urine cytology as a complementary method to cystoscopy during follow-up for LG NMIBC. Methods: Patients diagnosed with primary LG TaT1 bladder cancer (BC) between 2010 and 2020 were included. Patients were stratified according to the EAU NMIBC scoring model. Urine cytology was performed during follow-up cystoscopy. The outcomes of the study were BC recurrence and upgrading to high-grade (HG). Cytology utility was established by assessing whether its result led to management change. Results: We included 337 patients with LG TaT1 BC. EAU risk group distribution was low in 262 (77.7%), intermediate in 57 (16.9%), and high-risk in 18 (5.3%) cases. With a median follow-up of 5 years, 166 (49.3%) patients experienced recurrence. Cystoscopy was positive in 154 (92.8%) and suspicious in 12 (7.2%) cases. Urine cytology was positive in 33 (19.9%) cases but only changed management in 3 (0.89%), all with suspicious cystoscopy. Positive cytology at first recurrence was associated with higher risk of upgrading during follow-up (HR 2.781, p = 0.006) and lower upgrading-free survival (p = 0.001). Conclusion: The role of urine cytology to detect first recurrences during follow-up for primary LG TaT1 NMIBC might be limited to patients with non-conclusive lesions in the cystoscopy. A positive cytology at first recurrence is associated with a higher risk of upgrading to HG BC during follow-up.

Background: The interaction between cancer cells and cancer-associated fibroblasts (CAFs) is a key determinant of the rapid progression, high invasiveness, and chemoresistance of aggressive desmoplastic cancers such as pancreatic ductal adenocarcinoma (PDAC). Tumor cells are known to reprogram fibroblasts into CAFs by secreting transforming growth factor beta (TGF-β), amongst other cytokines. In turn, CAFs produce soluble factors that promote tumor-cell invasiveness and chemoresistance, including TGF-β itself, which has a major role in myofibroblastic CAFs. Such a high level of complexity has hampered progress toward a clear view of the TGFβ signaling loop between stromal fibroblasts and PDAC cells. Methods: Here, we tackled this issue by using co-culture settings that allow paracrine signaling alone (transwell systems) or paracrine and contact-mediated signaling (3D spheroids). Results: We found that TGF-β is critically involved in the activation of normal human fibroblasts into alpha-smooth muscle actin (α-SMA)-positive CAFs. The TGF-β released by CAFs accounted for the enhanced proliferation and resistance to gemcitabine of PDAC cells. This was accompanied by a partial epithelial-to-mesenchymal transition in PDAC cells, with no increase in their migratory abilities. Nevertheless, 3D heterospheroids comprising PDAC cells and fibroblasts allowed monitoring the pro-invasive effects of CAFs on cancer cells, possibly due to combined paracrine and physical contact-mediated signals. Conclusions: We conclude that TGF-β is only one of the players that mediates the communication between PDAC cells and fibroblasts and controls the acquisition of aggressive phenotypes. Hence, these advanced in vitro models may be exploited to further investigate these events and to design innovative anti-PDAC therapies.

Background: Recent research underscores a crucial connection between circadian rhythm disruption and cancer promotion, highlighting an urgent need for attention. Objectives: Explore the molecular mechanisms by which modern lifestyle factors—such as artificial light exposure, shift work, and dietary patterns—affect cortisol/melatonin regulation and cancer risk. Methods: Employing a narrative review approach, we synthesized findings from Scopus, Google Scholar, and PubMed to analyze lifestyle impacts on circadian health, focusing on cortisol and melatonin chronobiology as molecular markers. We included studies that documented quantitative changes in these markers due to modern lifestyle habits, excluding those lacking quantitative data or presenting inconclusive results. Subsequent sections focused solely on articles that quantified the effects of circadian disruption on adipogenesis and tumor microenvironment modifications. Results: This review shows how modern habits lead to molecular changes in cortisol and melatonin, creating adipose microenvironments that support cancer development. These disruptions facilitate immune evasion, chemotherapy resistance, and tumor growth, highlighting the critical roles of cortisol dysregulation and melatonin imbalance. Conclusions: Through the presented findings, we establish a causal link between circadian rhythm dysregulation and the promotion of certain cancer types. By elucidating this relationship, the study emphasizes the importance of addressing lifestyle factors that contribute to circadian misalignment, suggesting that targeted interventions could play a crucial role in mitigating cancer risk and improving overall health outcomes.

In the original publication […]

Background: Humans cannot avoid plastic exposure due to its ubiquitous presence in the natural environment. The waste generated is poorly biodegradable and exists in the form of MPs, which can enter the human body primarily through the digestive tract, respiratory tract, or damaged skin and accumulate in various tissues by crossing biological membrane barriers. There is an increasing amount of research on the health effects of MPs. Most literature reports focus on the impact of plastics on the respiratory, digestive, reproductive, hormonal, nervous, and immune systems, as well as the metabolic effects of MPs accumulation leading to epidemics of obesity, diabetes, hypertension, and non-alcoholic fatty liver disease. MPs, as xenobiotics, undergo ADMET processes in the body, i.e., absorption, distribution, metabolism, and excretion, which are not fully understood. Of particular concern are the carcinogenic chemicals added to plastics during manufacturing or adsorbed from the environment, such as chlorinated paraffins, phthalates, phenols, and bisphenols, which can be released when absorbed by the body. The continuous increase in NMP exposure has accelerated during the SARS-CoV-2 pandemic when there was a need to use single-use plastic products in daily life. Therefore, there is an urgent need to diagnose problems related to the health effects of MP exposure and detection. Methods: We collected eligible publications mainly from PubMed published between 2017 and 2024. Results: In this review, we summarize the current knowledge on potential sources and routes of exposure, translocation pathways, identification methods, and carcinogenic potential confirmed by in vitro and in vivo studies. Additionally, we discuss the limitations of studies such as contamination during sample preparation and instrumental limitations constraints affecting imaging quality and MPs detection sensitivity. Conclusions: The assessment of MP content in samples should be performed according to the appropriate procedure and analytical technique to ensure Quality and Control (QA/QC). It was confirmed that MPs can be absorbed and accumulated in distant tissues, leading to an inflammatory response and initiation of signaling pathways responsible for malignant transformation.