Volume 27, Issue 3

Cancer is a leading global cause of death, yet early detection and treatment are vital for enhancing patients’ lives. In recent years, scientists have been studying tumor biomarkers to help diagnose and predict the outcome of cancer. However, current biomarkers have limitations, so researchers are on the hunt for new ones to make tumor diagnosis more accurate. When tumor cells enter the bloodstream, they interact with different types of blood cells and platelets. During these interactions, platelets pick up molecules from the tumor cells, such as proteins, genetic material, and other substances. This results in alterations to the RNA and protein profiles of the platelets, forming tumor-educated platelets (TEPs). These TEPs are associated with the progression and spread of cancer due to their interactions with tumor cells. This review aims to provide a comprehensive look at recent research on TEPs as potential biomarkers for cancer. It will explore how TEPs are formed, their interactions with tumor cells, and the changes in their genetic and protein makeup, as well as their clinical importance. The aim is to provide novel insights for formulating strategies to prevent and treat cancer.

Mitochondria, the ‘powerhouses’ of cells, primarily produce ATP and also regulate homeostasis, apoptosis, and metabolism. In recent years, research advancements in oncology have highlighted the pivotal role of mitochondria in tumor initiation, progression, and therapeutic response. This review aims to provide a comprehensive summary of the latest research progress on mitochondrial functions in oncology, systematically discussing the mechanisms of mitochondrial dysfunction, metabolic reprogramming, and advances in mitochondrial-targeted therapies. Additionally, the complex role of mitochondria in tumor immunity is analyzed. Through integrated analysis and summary, this review seeks to reveal the significance of these findings in advancing basic cancer research and their potential implications for clinical applications, thereby offering new insights and directions for future cancer treatment strategies.

Cancer remains one of the leading causes of global mortality, with dysregulated epigenetic regulators playing pivotal roles in tumorigenesis. Among these, Jumonji C domain-containing protein 5 (JMJD5/KDM8), an assigned protein hydroxylase/histone demethylase, exhibits context-dependent oncogenic or tumor-suppressive functions across malignancies. While JMJD5 is significantly overexpressed in breast, colon, oral squamous cell carcinoma, prostate cancer, and atypical meningiomas, its downregulation is observed in liver and lung cancers, highlighting its paradoxical roles in cancer biology. This review systematically examines JMJD5’s multifaceted mechanisms in tumor progression, including its regulation of apoptosis, modulation of glucose metabolism, promotion of metastatic dissemination, and acceleration of cell cycle progression. We further discuss the therapeutic implications of JMJD5 targeting, emphasizing its potential as a novel epigenetic vulnerability for precision oncology strategies.

Objectives Older studies failed to establish a link between estrogen receptor (ER) expression and pancreatic adenocarcinoma, with findings either statistically insignificant or contradictory. The recent discovery of two distinct isoforms, namely ER-α and ER-β, with potentially differential expression in various pancreatic cells and with radically different effects, might explain preexisting contradictions. Therefore, the identification of two new ER types necessitates a reassessment of their role in the development and prognosis of pancreatic adenocarcinoma. This study aimed to investigate their differential expression in benign and malignant pancreatic lesions. Methods A case-matched study was conducted comparing benign and malignant pancreatic lesions in patients who underwent surgery at University Hospital ‘Aretaieio’, a tertiary referral centre for pancreatic disease. The expression of ER-α and ER-β receptors was assessed by immunohistochemistry and scored using two established scoring systems. Data regarding age, gender, histological diagnosis, grade, TNM stage, adjuvant treatment, follow-up, recurrence, and survival were recorded, and respective correlations were assessed. Results ER-α was detected in 31.25 % of benign tumours but not in any malignant tumours (p=0.003). ER-β was positive in 31.25 % of benign and 37.50 % of malignant tumours (p=0.757). Disease-free survival (p=0.910) and overall survival (p=0.623) were similar between ER-β negative and ER-β positive patients. Conclusions Pancreatic adenocarcinomas do not express ER-α, which might explain the failure of earlier trials targeting these receptors, but they do express ER-β at a considerable rate. Differences in the expression of ER-α and ER-β can be used to distinguish benign and malignant lesions. Moreover, further studies delineating the molecular function of ER-β and assessing it as a potential therapeutic target can lead to improved clinical outcomes.

Objectives One of the main participants in maintaining the redox balance is glutathione (GSH), the metabolism of which directly depends on the activity of gamma-glutamyltransferase (GGT), and the content of amino acids cysteine (Cys), methionine (Met), glutamine (Gln), glutamic acid (Glu), and glycine (Gly). This work aimed to investigate the relationship between salivary GGT activity in patients with breast cancer and the state of redox homeostasis. Methods The case-control study included volunteers with breast cancer (n=660), non-malignant breast pathologies (n=134), and a control group (n=127). Analysis of GGT activity and amino acid content in saliva was performed in all patients strictly before treatment, and in 139 patients, the study was repeated 4 weeks after surgical treatment. GGT activity was determined by the Zaits-Persin kinetic method. The concentration of amino acids (Cys, Met, Gln, Glu, and Gly) was determined using high-performance liquid chromatography. Results In breast cancer and fibroadenomas, antioxidant protection was activated and salivary GGT levels increased (+5.6 % in fibroadenomas, +11.3 % in breast cancer, p<0.0001). The highest salivary GGT activity was observed in the luminal hormone-negative breast cancer subgroups (+19.7 %, p<0.0001). This may indicate the sufficiency of metabolic resources to activate the antioxidant system in less aggressive luminal subtypes. In the non-luminal (+12.4 %, р=0.0054) and TNBC (+17.1 %, p<0.0001) subgroups, salivary GGT activity was close to normal values. Probably, in a more aggressive process, with depletion of biological resources, and more pronounced metabolic reprogramming of cancer cells, GSH synthesis is sharply reduced, which is expressed in a change in the amino acid balance. After surgery, salivary GGT activity decreased with the preservation of the residual metabolic pattern of the corresponding breast cancer phenotype. Conclusion The analysis of salivary GGT activity serves as a valuable tool for elucidating metabolic changes associated with breast cancer, including its potential application in post-treatment monitoring.

Objectives The abnormal metabolism of cancer cells, referred to as the Warburg effect, creates acidic tumor microenvironments (TME) that can contribute to treatment resistance and cancer progression. “Alkalization therapy”, which involves dietary changes, aims to reduce acidity by lowering the potential renal acid load. This study aims to analyze 5-year survival rates of cancer patients undergoing alkalization therapy and compare survival rates among various urine pH levels. Methods A total of 1,100 patients with stage IV cancers who first visited Karasuma Wada Clinic between January 2014 and December 2023 were retrospectively analyzed. The Kaplan–Meier method, log-rank test, and Cox proportional hazards model were used for statistical analyses. Results The overall 5-year survival rate was 37.7 %, including 7.9 % for pancreatic cancer, 44.3 % for breast cancer, and 48.6 % for non-small cell lung cancer (NSCLC). For pancreatic cancer, urine pH was the only significant prognostic factor, with a hazard ratio of 0.55 (95 % CI: 0.36–0.83, p=0.004). The 5-year survival rates of patients categorized by urine pH levels (pH≤5.5, 5.5<pH<7.5, and pH≥7.5) showed significant differences in patients with pancreatic and breast cancer (p<0.0001 and p=0.009, respectively). For NSCLC patients, a cutoff urine pH of 5.5 (≤5.5 vs. >5.5) showed a significant difference in overall survival (p=0.0434). Conclusions Alkalization therapy is a promising cancer treatment that complements standard therapies. Raising urine pH may optimize TME and enhance survival outcomes.

Objectives Prophylactic salpingo-oophorectomy in BRCA -mutated patients reduces the risk of breast and ovarian cancer. This study aimed to compare peri-operative outcomes of BRCA -mutated patients who underwent prophylactic salpingo-oophorectomy via traditional laparoscopy or percutaneous assisted laparoscopy. Methods In this single-center retrospective cohort study, BRCA -mutated patients submitted to laparoscopic prophylactic bilateral salpingo-oophorectomy were enrolled. We compared traditional laparoscopy and percutaneous-assisted laparoscopy, which was performed using the Percuvance grasp. Results We enrolled 59 patients submitted to prophylactic salpingo-oophorectomy from September 2017 to September 2022. Thirty-nine underwent a conventional laparoscopic procedure (LPS) and 20 a percutaneous-assisted laparoscopy (PERC). Similar clinical characteristics were found in the two groups, furthermore, no differences were noticed in terms of peri-operative complication, intraoperative blood loss (p=0.7), and hospital stay (p=0.6). A significantly lower post-operative pain, using VAS score, was noticed in the PERC group compared with the LPS group, on both the first and second days after surgery. Moreover, better cosmetic results have been highlighted in the PERC group. Conclusions Percutaneous-assisted laparoscopy seems an effective and safe procedure for laparoscopic prophylactic adnexectomy in BRCA -mutated patients. Furthermore, the percutaneous procedure showed better aesthetic outcomes and reduced post-operative pain, compared to traditional laparoscopy.

Objectives Cervical cancer poses a significant health threat. While acetyl-CoA acetyltransferase 2 ( ACAT2 ) gene is known to promote hepatocellular carcinoma progression, its role in cervical cancer remains unclear. This study aims to elucidate the function of ACAT2 in cervical cancer. Methods ACAT2 expression in cervical cancer and adjacent non-cancerous tissues was assessed using Western blotting and qPCR. The correlation between ACAT2 expression levels and patients’ pathological features as well as survival outcomes was evaluated. The effects of ACAT2 knockdown on cell proliferation and migration were tested in C33a and HeLa cells. TRULI, an inhibitor targeting LATS1 , a downstream gene of ACAT2 , was used to treat ACAT2 -overexpressing C33a and HeLa cells to assess its impact on these processes. Results ACAT2 exhibited significantly higher expression in cervical cancer tissues compared to adjacent non-cancerous tissues (p<0.0001). Elevated ACAT2 expression was significantly correlated with the pathological grading (p<0.05) and associated with poor overall survival (OS) (p<0.05) in patients. ACAT2 knockdown inhibited the proliferative activity and migration of C33a and HeLa cells and induced apoptosis in both cells. Furthermore, by inhibiting the expression of the key downstream gene LATS1 , the proliferation and migration of ACAT2 -overexpressing C33a and HeLa cells were significantly reduced, while also inducing apoptosis in both overexpressing cells. Conclusions ACAT2 plays a proactive role in regulating the development and progression of cervical cancer, likely through its involvement with the LATS1 in its downstream pathway. Consequently, ACAT2 represents a promising potential biomarker and therapeutic target for cervical cancer.

Objectives Hyperthermia enhances tumor sensitivity to treatments like radiotherapy and chemotherapy, but high temperatures (42–45 °C) can damage normal tissues, especially heat-sensitive neuronal cells. This study aims to examine the effects of mild hyperthermia (39–41 °C) on glioblastoma (GBM) and non-small cell lung cancer (NSCLC) cell lines to determine its therapeutic potential while minimizing normal tissue damage. Methods GBM (U373, A172) and NSCLC (A549, H460) cells were exposed to mild hyperthermia for up to 72 h. Cell viability was assessed using the MTT assay, while apoptosis was analyzed via annexin V staining and cleaved-PARP expression through flow cytometry and Western blotting. Clonogenic survival was evaluated to determine long-term effects. Results Cell viability decreased in a temperature- and time-dependent manner, with A549 cells exhibiting a ∼40 % reduction after 72 h at 40 °C. Apoptosis markers, annexin V and cleaved-PARP, showed time-dependent increases, confirming apoptotic induction (p<0.01). Clonogenic assays demonstrated significantly lower survival fractions following prolonged exposure, indicating reduced tumorigenic potential. Conclusions Mild hyperthermia effectively reduces cancer cell viability and induces apoptosis in GBM and NSCLC cells while minimizing potential damage to normal tissues. These findings suggest that optimizing temperature and exposure time can enhance hyperthermia’s therapeutic efficacy, making it a promising strategy for safer and more effective cancer treatment.

Objectives Orbital mucosa-associated lymphoid tissue (MALT) lymphoma with amyloidosis is an uncommon condition. This study presents three cases of this rare disease, to provide insights into its clinical manifestation, clinicopathological features, treatment options, and prognosis. Case presentation This study reports three cases of orbital MALT lymphoma with amyloidosis. All patients exhibited proptosis, and imaging findings revealed orbital masses. Furthermore, two cases were potentially associated with IgG4-related ophthalmic disease. The diagnosis of all patients was confirmed via immunohistochemical (IHC) analysis of the biopsy samples. One patient exhibited space-occupying lesions in the lungs and kidneys. In addition, one patient underwent orbital radiotherapy, and a 1-year follow-up revealed a reduction in the orbital mass volume. Another patient underwent systemic chemotherapy, but imaging at the eight-month follow-up revealed no substantial changes in the orbital or systemic lesions. Conclusions The coexistence of orbital MALT lymphoma and amyloidosis presents diagnostic challenges because of its rarity and the involvement of two distinct conditions. Immunohistochemistry (IHC) is a key tool for establishing a definitive diagnosis. Surgery is the most commonly employed treatment method. Although it does not provide a definitive cure, the primary importance lies in obtaining biopsy samples for precise diagnosis and reducing the tumor burden to alleviate the mass effects. Orbital radiotherapy remains a key treatment option. However, in cases with systemic involvement, systemic chemotherapy or alternative therapies may be prioritized to manage systemic symptoms effectively.

Esophageal cancer is a highly aggressive disease with a poor prognosis, significantly impacting patients’ quality of life through symptoms such as difficulty in swallowing, malnutrition, and overall deterioration in health. Palliative care plays a crucial role, as median survival in advanced cases is typically limited to only a few months. This mini paper evaluates palliative treatment options for the management of swallowing difficulties, including self-expanding metal stents, internal radiation therapy, external beam radiation therapy, and combined chemotherapy and radiation therapy. It aims to clearly define the clinical significance and role of external beam radiation therapy as a palliative treatment option for swallowing difficulties in advanced esophageal cancer. Combining radiation therapy with chemotherapy or exploring novel radiation fractionation schedules may further improve treatment outcomes. The perspective summarizes recent clinical reports on the use of external beam radiation therapy in the palliative management of swallowing difficulties, compares its effectiveness with other treatment modalities, and discusses its potential to improve patient care through integrated therapeutic approaches and emerging strategies.

Endometriosis and endometriosis-associated ovarian cancer (EAOC) are related yet different gynecological conditions, often with EAOC developing upon endometriosis. This latter significantly increases the risk for ovarian cancer, especially endometrioid and clear cell types. Detecting EAOC poses a notable challenge due to its frequently asymptomatic initial phases and the absence of reliable screening methods, emphasizing the necessity for better diagnostic techniques. MicroRNAs (miRNAs) have been recognized as potential biomarkers for both endometriosis and EAOC. The research identified specific miRNAs including miR-21, miR-200, and miR-145, as exhibiting dysregulation in both conditions, indicating the early onset of these alterations and suggesting their potential involvement in the process of malignant transformation to EAOC. Furthermore, diagnostics using miRNAs hold great promise for non-invasive personalized assessments, leading to earlier detection and more effective individualized treatment plans. In this short perspective paper, we aim to highlight the potential link between endometriosis and EAOC discussing the possibility of early diagnosis through the evaluation of miRNAs in the blood of patients affected by these conditions.