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The incidence of breast and colorectal cancers is well established in studies, but the synchronous occurrence of the two types of tumors is a rarity. In general, they are discovered during screening investigations following the diagnosis of an initial tumor. Objective: Our aim is to describe the main diagnostic and therapeutic challenges for synchronous breast and colorectal tumors. Materials and methods: We performed a systematic review of the literature for cases or case series, using established keywords (synchronous breast and colon tumor and synonyms) for the period of 1970–2023. Five reviewers independently screened the literature, extracted data, and assessed the quality of the included studies. The results were processed according to the PRISMA 2020 guidelines. Results: A total of 15 cases were included in the study, including 2 males (age 50 and 57) and 13 females (median age 60, with range from 40 to 79). In a vast majority of the cases, the diagnosis of synchronous tumor was prompted by the first tumor’s workup. The first diagnosed tumor was colorectal in nine cases and a breast tumor in six cases. The most common histopathological type of breast tumor was invasive ductal carcinoma, and the colon tumors were exclusively adenocarcinomas. All cases had a surgical indication for both breast and colorectal tumor, except one case, in which the breast tumor had multiple metastasis. In four cases, the surgery was performed concomitantly (colectomy and mastectomy). In three cases, surgery was initially carried out for the breast tumor, followed by colon surgery. Oncological treatment was indicated depending on the tumor stage. Conclusions: For the treatment of synchronous tumors, the Tumor Board (T.B) decision is mandatory and must be personalized for each patient. Developing new methods of treatment and investigation may play an important role in the future for understanding synchronous tumor development, incidence, and outcome. Full article

Colorectal cancer remains a major global health concern. Colonoscopy, the gold-standard colorectal cancer diagnostic, relies on the visual detection of lesions and necessitates invasive biopsies for confirmation. Alternative diagnostic methods, based on nanomedicine, can facilitate early detection of malignancies. Here, we examine the uptake of surface-enhanced Raman scattering nanoparticles (SERS NPs) as a marker for intestinal tumor detection and imaging using an established Drosophila melanogaster model for gut disease. Young and old Oregon-R and w¹¹¹⁸ flies were orally administered SERS NPs and scanned without and upon gut lumen clearance to assess nanoparticle retention as a function of aging. Neither young nor old flies showed significant NP retention in their body after gut lumen clearance. Moreover, tumorigenic flies of the esg-Gal4/UAS-Ras^V12 genotype were tested for SERS NP retention 2, 4 and 6 days after Ras^V12 oncogene induction in their midgut progenitor cells. Tumorigenic flies showed a statistically significant NP retention signal at 2 days, well before midgut epithelium impairment. The signal was then visualized in scans of dissected guts revealing areas of NP uptake in the posterior midgut region of high stem cell activity. Full article

Metronomic chemotherapy with cyclophosphamide (Cpp) has shown promising results in cancer protocols. These lower and prolonged doses have antiangiogenic, pro-cytotoxic, and moderate secondary effects. Molecular iodine (I₂) reduces the viability of cancer cells and, with chemotherapeutic agents, activates the antitumoral immune response and diminishes side effects. The present work evaluates the adjuvant of oral I₂ with Cpp using a murine model of mammary cancer. Female Sprague Dawley rats with 7,12-dimethylbenzantracene-induced tumors received Cpp intraperitoneal (50 and 70 mg/kg two times/week, iCpp50 and iCpp70) and oral (0.03%; 50 mg/Kg; oCpp50) doses. I₂ (0.05%, 50 mg/100 mL) and oCpp50 were offered in drinking water for three weeks. iCpp70 was the most efficient antitumoral dose but generated severe body weight loss and hemorrhagic cystitis (HC). I₂ prevented body weight loss, exhibited adjuvant actions with Cpp, decreasing tumor growth, and canceled HC mechanisms, including decreases in vascular endothelial growth factor (VEGF) and Survivin expression. oCpp50 + I₂ diminished angiogenic signals (CD34, vessel-length, and VEGF content) and proinflammatory cytokines (interleukin-10 and tumor necrosis factor-alpha) and increased cytotoxic (lymphocytic infiltration, CD8⁺ cells, Tbet, and interferon-gamma) and antioxidant markers (nuclear erythroid factor-2 and glutathione peroxidase). I₂ enhances the effectiveness of oCpp, making it a compelling candidate for a clinical protocol. Full article

Immunotherapy has emerged as an attractive option for patients with relapsed or refractory high-risk neuroblastoma (HRNB). Neuroblastoma (NB), a sympathetic nervous system cancer arising from an embryonic neural crest cell, is heterogeneous clinically, with outcomes ranging from an isolated abdominal mass that spontaneously regresses to a widely metastatic disease with cure rates of about 50% despite intensive multimodal treatment. Risk group stratification and stage-adapted therapy to achieve cure with minimal toxicities have accomplished major milestones. Targeted immunotherapeutic approaches including monoclonal antibodies, vaccines, adoptive cellular therapies, their combinations, and their integration into standard of care are attractive therapeutic options, although curative challenges and toxicity concerns remain. In this review, we provide an overview of immune approaches to NB and the tumor microenvironment (TME) within the clinical translational framework. We propose a novel T cell-based therapeutic approach that leverages the unique properties of tumor surface antigens such as ganglioside GD2, incorporating specific monoclonal antibodies and recent advancements in adoptive cell therapy. Full article

Ovarian cancer is one of the leading causes of cancer deaths among women. There is an ongoing need to develop new biomarkers and targeted therapies to improve patient outcomes. One of the most critical research areas in ovarian cancer is identifying tumor microenvironment (TME) functions. TME consists of tumor-infiltrating immune cells, matrix, endothelial cells, pericytes, fibroblasts, and other stromal cells. Tumor invasion and growth depend on the multifactorial crosstalk between tumor cells and immune cells belonging to the TME. MiRNAs, which belong to non-coding RNAs that post-transcriptionally control the expression of target genes, regulate immune responses within the TME, shaping the landscape of the intrinsic environment of tumor cells. Aberrant expression of miRNAs may lead to the pathological dysfunction of signaling pathways or cancer cell-regulatory factors. Cell-to-cell communication between infiltrating immune cells and the tumor may depend on exosomes containing multiple miRNAs. MiRNAs may exert both immunosuppressive and immunoreactive responses, which may cause cancer cell elimination or survival. In this review, we highlighted recent advances in the field of miRNAs shaping the landscape of immune cells in the TME. Full article

The diselenide bond has attracted intense interest for drug delivery systems (DDSs) for tumor chemotherapy, owing to it possessing higher redox sensitivity than the disulfide one. Various redox-responsive diselenide-containing carriers have been developed for chemotherapeutics delivery. However, the premature drug leakage from these DDSs was significant enough to cause toxic side effects on normal cells. Here, a pH/redox co-triggered degradable polyprodrug was designed as a drug self-delivery system (DSDS) by incorporating drug molecules as structural units in the polymer main chains, using a facile one-pot two-step approach. The proposed PDOX could only degrade and release drugs by breaking both the neighboring acid-labile acylhydrazone and the redox-cleavable diselenide conjugations in the drug’s structural units, triggered by the higher acidity and glutathione (GSH) or reactive oxygen species (ROS) levels in the tumor cells. Therefore, a slow solubility-controlled drug release was achieved for tumor-specific chemotherapy, indicating promising potential as a safe and efficient long-acting DSDS for future tumor treatment. Full article

Keratinocytes are major cellular components of the skin and are strongly involved in its homeostasis. Oncogenic events, starting mainly from excessive sun exposure, lead to the dysregulation of their proliferation and differentiation programs and promote the initiation and progression of non-melanoma skin cancers (NMSCs). Primary melanomas, which originate from melanocytes, initiate and develop in close interaction with keratinocytes, whose role in melanoma initiation, progression, and immune escape is currently being explored. Recent studies highlighted, in particular, unexpected modes of communication between melanocytic cells and keratinocytes, which may be of interest as sources of new biomarkers in melanomagenesis or potential therapeutic targets. This review aims at reporting the various contributions of keratinocytes in skin basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, with a greater focus on the latter in order to highlight some recent breakthrough findings. The readers are referred to recent reviews when contextual information is needed. Full article

Glioblastoma multiforme (GBM) is the most severe form of brain cancer and presents unique challenges to developing novel treatments due to its immunosuppressive milieu where receptors like programmed death ligand 1 (PD-L1) are frequently elevated to prevent an effective anti-tumor immune response. To potentially shift the GBM environment from being immunosuppressive to immune-enhancing, we engineered a novel nanovehicle from reduced graphene oxide quantum dot (rGOQD), which are loaded with the immunomodulatory drug resiquimod (R848) and conjugated with an anti-PD-L1 antibody (aPD-L1). The immunomodulatory rGOQD/R8/aPDL1 nanoparticles can actively target the PD-L1 on the surface of ALTS1C1 murine glioblastoma cells and release R848 to enhance the T-cell-driven anti-tumor response. From in vitro experiments, the PD-L1-mediated intracellular uptake and the rGOQD-induced photothermal response after irradiation with near-infrared laser light led to the death of cancer cells and the release of damage-associated molecular patterns (DAMPs). The combinational effect of R848 and released DAMPs synergistically produces antigens to activate dendritic cells, which can prime T lymphocytes to infiltrate the tumor in vivo. As a result, T cells effectively target and attack the PD-L1-suppressed glioma cells and foster a robust photothermal therapy elicited anti-tumor immune response from a syngeneic mouse model of GBM with subcutaneously implanted ALTS1C1 cells. Full article

The PTEN tumor suppressor is frequently targeted in tumors and patients with PTEN hamartoma tumor syndrome (PHTS) through nonsense mutations generating premature termination codons (PTC) that may cause the translation of truncated non-functional PTEN proteins. We have previously described a global analysis of the readthrough reconstitution of the protein translation and function of the human canonical PTEN isoform by aminoglycosides. Here, we report the efficient functional readthrough reconstitution of the PTEN translational isoform PTEN-L, which displays a minimal number of PTC in its specific N-terminal extension in association with disease. We illustrate the importance of the specific PTC and its nucleotide proximal sequence for optimal readthrough and show that the more frequent human PTEN PTC variants and their mouse PTEN PTC equivalents display similar patterns of readthrough efficiency. The heterogeneous readthrough response of the different PTEN PTC variants was independent of the length of the PTEN protein being reconstituted, and we found a correlation between the amount of PTEN protein being synthesized and the PTEN readthrough efficiency. Furthermore, combination of aminoglycosides and protein synthesis inducers increased the readthrough response of specific PTEN PTC. Our results provide insights with which to improve the functional reconstitution of human-disease-related PTC pathogenic variants from PTEN isoforms by increasing protein synthesis coupled to translational readthrough. Full article

Tongue squamous cell carcinoma (TSCC) occurs frequently in the oral cavity, and because of its high proliferative and metastatic potential, it is necessary to develop a novel treatment for it. We have reported the importance of the inhibition of the periostin (POSTN) pathological splicing variant, including exon 21 (PN1-2), in various malignancies, but its influence is unclear in tongue cancer. In this study, we investigated the potential of POSTN exon 21-specific neutralizing antibody (PN21-Ab) as a novel treatment for TSCC. Human PN2 was transfected into the human TSCC (HSC-3) and cultured under stress, and PN2 was found to increase cell viability. PN2 induced chemotherapy resistance in HSC-3 via the phosphorylation of the cell survival signal Akt. In tissues from human TSCC and primary tumors of an HSC-3 xenograft model, PN1-2 was expressed in the tumor stroma, mainly from fibroblasts. The intensity of PN1-2 mRNA expression was positively correlated with malignancy. In the HSC-3 xenograft model, CDDP and PN21-Ab promoted CDPP’s inhibition of tumor growth. These results suggest that POSTN exon 21 may be a biomarker for tongue cancer and that PN21-Ab may be a novel treatment for chemotherapy-resistant tongue cancer. The treatment points towards important innovations for TSCC, but many more studies are needed to extrapolate the results. Full article

Anaplastic lymphoma kinase (ALK) is detected in both normal and oncological developmental tissues. Among ALK-related tumors, superficial ALK-rearranged myxoid spindle cell neoplasm (SAMS) is a rare, soft tissue tumor characterized by the immunophenotypical co-expression of CD34 and S100. Here, we describe a patient with this rare tumor and outline its clinical and radiological characteristics. A 28-year-old woman with diabetes, hypertension, and panic disorder presented with discomfort caused by a rubbery mass on the left buttock that had persisted for 10 years. Computed tomography revealed a multilobulated hypodense mass with small internal enhancing foci, posing challenges for the exact diagnosis of the lesion. The entire lesion was excised with clear resection margins. An 8.0 × 6.0 cm, well-circumscribed tumor with a lobular growth pattern was observed in the deep subcutaneous tissue. Light microscopy revealed epithelioid, ovoid, and spindle-shaped cells with a reticular cordlike pattern. Immunohistochemistry results were positive for S100, CD34, and vimentin. Break-apart fluorescence in situ hybridization assay results for ALK were also positive. These findings were consistent with those of SAMS. This case suggests that SAMS should be considered when identifying large nonspecific masses during clinical and imaging evaluation. Full article

Chronic lymphocytic leukemia (CLL) is the most common human leukemia. The disease is caused by abnormal proliferation and development of lymphocytes and their precursors in the blood and bone marrow (BM). Recent studies have shown that the CLL’s clinical course and outcome depend not only on genetic but also epigenetic factors. MicroRNAs (miRNAs) are involved in the development of hematological tumors, including CLL. The aim of this study is to identify the miRNA expression profile in CLL and determine the role of miRNAs in biological pathways associated with leukemogenesis in CLL. The following samples were used in this study: (1) samples obtained by sternal puncture and aspiration biopsy of BM (n = 115). They included samples from 21 CLL patients with anemia and indications for therapy and 45 CLL patients without anemia and with indications for therapy. The control group for the CLL BM samples consisted of patients with non-cancerous blood diseases (n = 35). (2) Lymph node (LN) samples (n = 20) were collected from CLL patients. The control group for the CLL LN samples consisted of patients with lymphadenopathy (n = 37). All cases were patients before treatment. We demonstrated a significant upregulation of miRNA-34a and miRNA-150 in CLL BM samples (p < 0.05) and downregulation of miRNA-451a in CLL LN samples (p < 0.05). We noted a dynamic increase in the levels of miRNA-150 and miRNA-34a in BM at various stages of tumor progression of CLL. We concluded that a dynamic picture of clinical manifestations of CLL closely correlates with changes in epigenetic characteristics of the tumor. Progression of the lymphoproliferative process and indications for cytoreductive therapy are associated with changes in the miRNA profile generated by cancer cells in different sites of clonal expansion. Full article

Background/Objectives: Colorectal cancer (CRC) is still accompanied by significant mortality, which poses the necessity of novel markers to predict treatment success and patient survival. This study aims to evaluate the prognostic and survival impact of flowytometry (FC) in CRC patients. Methods: In this prospective study, 106 surgically resectable CRC patients were included. Tissue specimens from tumor and normal mucosa were collected and analyzed by FC. DNA and tumor index were calculated. In a subgroup of 46 patients, the CD26 expression on tumor cells was estimated. These parameters were compared with patients’ tumor characteristics as stage, histology data, responsiveness to treatment, metastasis/recurrence, and, finally, patients’ survival to identify possible new biomarkers. Results: The overall survival and the disease-specific survival in our study group was 76% and 72%, respectively, during the 7-year follow up period. Diploid tumors had better median survival than the aneuploid ones. The DNA index had significant correlation to the tumor index and response to neoadjuvant treatment. Similarly, the tumor index was also significantly related to the response to neoadjuvant treatment. Patients with a higher tumor index had worst survival rates. Surprisingly, CD26 levels were not associated with any of the parameters examined and were negatively related to tumor stage and differentiation. Conclusions: FC is a rapid and reliable method of cell analysis. In CRC, it has been used for prognostic and diagnostic purposes. In this study, we have shown that DNA and tumor index could become predictive biomarkers of tumor response to neoadjuvant treatment and survival of resectable CRC patients. Full article

Triple-negative breast cancer (TNBC), accounting for 15–20% of all breast cancers, has one of the poorest prognoses and survival rates. Metastasis, a critical process in cancer progression, causes most cancer-related deaths, underscoring the need for alternative therapeutic approaches. This study explores the anti-migratory, anti-invasive, anti-tumoral, and antimetastatic effects of copper coordination compounds Casiopeína IIIia (CasIIIia) and Casiopeína IIgly (CasIIgly) on MDA-MB-231 and 4T1 breast carcinoma cell lines in vitro and in vivo. These emerging anticancer agents, mixed chelate copper(II) compounds, induce apoptosis by generating reactive oxygen species (ROS) and causing DNA damage. Whole-transcriptome analysis via gene expression arrays indicated that subtoxic concentrations of CasIIIia upregulate genes involved in metal response mechanisms. Casiopeínas^® reduced TNBC cell viability dose-dependently and more efficiently than Cisplatin. At subtoxic concentrations (IC₂₀), they inhibited random and chemotactic migration of MDA-MB-231 and 4T1 cells by 50–60%, similar to Cisplatin, as confirmed by transcriptome analysis. In vivo, CasIIIia and Cisplatin significantly reduced tumor growth, volume, and weight in a syngeneic breast cancer model with 4T1 cells. Furthermore, both compounds significantly decreased metastatic foci in treated mice compared to controls. Thus, CasIIIia and CasIIgly are promising chemotherapeutic candidates against TNBC. Full article

Background: Objective quantitative texture characteristics may be helpful in salivary glandular tumor differential diagnosis. This study uses machine learning (ML) to explore and validate the performance of ultrasound (US) texture features in diagnosing salivary glandular tumors. Material and methods: 122 patients with salivary glandular tumors, including 71 benign and 51 malignant tumors, are enrolled. Representative brightness mode US pictures are selected for further Gray Level Co-occurrence Matrix (GLCM) texture analysis. We use a t-test to test the significance and use the receiver operating characteristic curve method to find the optimal cut-point for these significant features. After splitting 80% of the data into a training set and 20% data into a testing set, we use five machine learning models, k-nearest Neighbors (kNN), Naïve Bayes, Logistic regression, Artificial Neural Networks (ANNs) and supportive vector machine (SVM), to explore and validate the performance of US GLCM texture features in diagnosing salivary glandular tumors. Results: This study includes 49 female and 73 male patients, with a mean age of 53 years old, ranging from 21 to 93. We find that six GLCM texture features (contrast, inverse difference movement, entropy, dissimilarity, inverse difference and difference entropy) are significantly different between benign and malignant tumors (p < 0.05). In ML, the overall accuracy rates are 74.3% (95%CI: 59.8–88.8%), 94.3% (86.6–100%), 72% (54–89%), 84% (69.5–97.3%) and 73.5% (58.7–88.4%) for kNN, Naïve Bayes, Logistic regression, a one-node ANN and SVM, respectively. Conclusions: US texture analysis with ML has potential as an objective and valuable tool to make a differential diagnosis between benign and malignant salivary gland tumors. Full article