Tumor Mass Research Articles

Preoperative evaluation of red blood cell distribution width as a promising biomarker for discriminating between benign and malignant breast tumors and assessing breast cancer activity.

The red cell distribution width (RDW) has been recognized as a new prognostic factor in various pathophysiological states including breast cancers. The aim of this study was to compare the RDW values between patients diagnosed with benign and malignant breast tumors and to evaluate the potential of elevated RDW as a biomarker for breast cancer activity. A cross-sectional study compared RDW values in age-matched cohorts diagnosed with benign and malignant breast lesions and correlated them with prognostic factors for malignant breast tumors. The study excluded individuals with inflammatory disorders, pre-neoplastic disease, hematological disorders, or those taking immunosuppressive or anti-inflammatory medications. The RDW values were measured using an automated hematology analyzer. The study's statistical analysis was conducted using SPSS software at a significance level of 0.05. RDW demonstrated a statistically significant elevation in the cohort of patients with malignant breast tumors, those with metastatic breast tumors, a greater number of infiltrated axillary lymph nodes, larger tumor diameter, and a higher grade of the primary tumor mass. The findings of this study suggest that RDW has the potential to serve as a biomarker for assessing breast cancer activity and could offer substantial advantages in clinical contexts. The present study is not without limitations, and the authors suggest that a larger multicenter prospective study be conducted to further validate it's efficacy over an extended duration.

Multifocality in Testicular Cancer: Clinicopathological Correlations and Prognostic Implications.

There are limited data regarding the significance of multifocality in testicular cancer patients. This study evaluated the relationship between multifocality and clinicopathological features determined at the time of radical orchiectomy. The study involved 280 consecutive patients who underwent radical orchiectomy between 2018 and 2023. Multifocality was defined as a distinct tumor focus characterized by a group of malignant cells > 1 mm, clearly differentiated from the primary tumor mass. Uni- and multivariate logistic regression analyses were employed to investigate the association between multifocality and histopathological parameters along with potential risk factors for clinical stages II + III. Multifocality was identified in 44 (15.7%) patients. Significantly smaller primary tumors were observed in subjects with multifocality (20.0 mm vs. 30.0 mm, p = 0.0001), while those exhibiting monofocality presented a markedly elevated rate of tumors exceeding 4 cm (40.3% vs. 18.2%, p = 0.005). Furthermore, multifocality was associated with a significantly higher rate of primary tumors < 2 cm (52.3% vs. 29.2%, p = 0.003). Univariate logistic regression analysis revealed a substantial decrease in the likelihood of multifocality occurrence in seminoma patients with tumors > 4 cm (OR = 0.38, p = 0.017). Meanwhile, in multivariate logistic regression, multifocality did not emerge as a significant risk factor for clinical stages II + III in either seminoma (p = 0.381) or non-seminoma (p = 0.672) cases. Our study suggests that multifocality holds no substantial prognostic relevance for clinically advanced disease in testicular cancer patients. The findings indicate that multifocality is associated with smaller primary tumors, particularly those measuring less than 2 cm.

Novel plasma-polymerized coating facilitates HeLa cell spheroid formation, exerting necroptosis via β-cyclodextrin-encapsulated resveratrol

Beta-cyclodextrins (β-CDs) comprise a pore for accommodating resveratrol (Res), thereby boosting its bioavailability. Res-incorporated β -CD (Res/CD) may be cytotoxic against both normal and cancer cells. Herein, we examined whether Res/CD exhibits anticancer activity against tumor spheroids, similar to in vivo tumor mass. To prepare three-dimensional spheroids, 1,1,1,3,5,7,7,7 octamethyl-3,5-bis(trimethylsiloxyl) tetrasiloxane (OMBTSTS) was deposited to the surface of the culture dish via plasma polymerization. We observed that HeLa cells grew as spheroids on the OMBTSTS-deposited surface at 20 W plasma power. Res/CD was delivered to the hypoxic core of the spheroid, inducing necrosis, whereas Res was not. Consistently, 10 μM Res alone was not cytotoxic to two-dimensional HeLa cells grown on a culture dish and three-dimensional spheroids. However, Res/CD promoted the necroptosis of spheroids, which were split into small fragments, ultimately inducing cell spheroid death. Collectively, our data suggest that nontoxic levels of Res/CD were efficiently delivered to the hypoxic core of tumor spheroids, promoting cell death. Therefore, Res/CD can be used as an effective anticancer drug. Moreover, the plasma-polymerized OMBTSTS modification technique provides insights into the efficient formation of spheroids in various cancer cell lines.

Neoadjuvant chemo- or chemo-radiation-therapy of pancreatic ductal adenocarcinoma differentially shift ECM composition, complement activation, energy metabolism and ribosomal proteins of the residual tumor mass.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, often diagnosed at stages that dis-qualify for surgical resection. Neoadjuvant therapies offer potential tumor regression and improved resectability. Although features of the tumor biology (e.g., molecular markers) may guide adjuvant therapy, biological alterations after neoadjuvant therapy remain largely unexplored. We performed mass spectrometry to characterize the proteomes of 67 PDAC resection specimens of patients who received either neoadjuvant chemo (NCT) or chemo-radiation (NCRT) therapy. We employed data-independent acquisition (DIA), yielding a proteome coverage in excess of 3500 proteins. Moreover, we successfully integrated two publicly available proteome datasets of treatment-naïve PDAC to unravel proteome alterations in response to neoadjuvant therapy, highlighting the feasibility of this approach. We found highly distinguishable proteome profiles. Treatment-naïve PDAC was characterized by enrichment of immunoglobulins, complement and extracellular matrix (ECM) proteins. Post-NCT and post-NCRT PDAC presented high abundance of ribosomal and metabolic proteins as compared to treatment-naïve PDAC. Further analyses on patient survival and protein expression identified treatment-specific prognostic candidates. We present the first proteomic characterization of the residual PDAC mass after NCT and NCRT, and potential protein candidate markers associated with overall survival. We conclude that residual PDAC exhibits fundamentally different proteome profiles as compared to treatment-naïve PDAC, influenced by the type of neoadjuvant treatment. These findings may impact adjuvant or targeted therapy options.

Brain-Decellularized ECM-Based 3D Myeloid Sarcoma Platform: Mimicking Adaptive Phenotypic Alterations in the Brain.

Leukemia circulates in the bloodstream and induces various symptoms and complications. Occasionally, these cells accumulate in non-marrow tissues, forming a tumor-like myeloid sarcoma (MS). When the blast-stage leukemia cells invade the brain parenchyma, intracranial MS occurs, leading to a challenging prognosis owing to the limited penetration of cytostatic drugs into the brain and the development of drug resistance. The scarcity of tissue samples from MS makes understanding the phenotypic changes occurring in leukemia cells within the brain environment challenging, thereby hindering development of effective treatment strategies for intracranial MS. This study presents a novel 3D in vitro model mimicking intracranial MS, employing a hydrogel scaffold derived from the brain-decellularized extracellular matrix in which suspended leukemia cells are embedded, simulating the formation of tumor masses in the brain parenchyma. This model reveals marked phenotypic changes in leukemia cells, including altered survival, proliferation, differentiation, and cell cycle regulation. Notably, proportion of dormant leukemia stem cells increases and expression of multidrug resistance genes is upregulated, leading to imatinib resistance, mirroring the pathological features of in vivo MS tissue. Furthermore, suppression of ferroptosis is identified as an important characteristic of intracranial MS, providing valuable insights for the development of targeted therapeutic strategies.

Intratumoral delivery of a highly active form of XCL1 enhances antitumor CTL responses through recruitment of CXCL9-expressing conventional type-1 dendritic cells.

Conventional type 1 dendritic cells (cDC1s) play a crucial role in antitumor immunity through the induction and activation of tumor-specific CD8+ cytotoxic T cells (CTLs). The chemokine XCL1 is a major chemotactic factor for cDC1s and its receptor XCR1 is selectively expressed on cDC1s. Here, we investigated the effect of intratumoral delivery of a highly active form of murine XCL1 (mXCL1-V21C/A59C) on cDC1-mediated antitumor immunity using a hydrophilic gel patch. The hydrophilic gel patch containing mXCL1-V21C/A59C increased cDC1 accumulation in the tumor masses and promoted their migration to the regional lymph nodes, resulting in enhanced induction of tumor-specific CTLs. Tumor-infiltrating cDC1s not only expressed XCR1 but also produced CXCL9, a ligand for CXCR3 which is highly expressed on CTLs and NK cells. Consequently, CTLs and NK cells were increased in the tumor masses of mice treated with mXCL1-V21C/A59C, while immunosuppressive cells such as monocyte-derived suppressive cells and regulatory T cells were decreased. We also confirmed that anti-CXCL9 treatment decreased the tumor infiltration of CTLs. The intratumoral delivery of mXCL1-V21C/A59C significantly decreased tumor growth and prolonged survival in E.G7-OVA and B16-F10 tumor-bearing mice. Furthermore, the antitumor effect of mXCL1-V21CA59C was enhanced in combination with anti-programmed cell death protein 1 treatment. Finally, using The Cancer Genome Atlas database, we found that XCL1 expression was positively correlated with tumor-infiltrating cDC1s and a better prognosis in melanoma patients. Collectively, our findings provide a novel therapeutic approach to enhance tumor-specific CTL responses through the selective recruitment of CXCL9-expressing cDC1s into the tumor masses.

MANAGEMENT OF CONJUNCTIVAL MELANOMA ARISING FROM PRIMARY ACQUIRED MELANOMA (PAM) : A CASE REPORT

Introduction : Conjunctival melanoma (CMM) is a rare but potentially a life threatening ocular malignancy. It is an aggressive pigmented tumor and the recurrence rate may be as high as 51% over 10 years.1,2 Surgical wide local excision of the tumour and cryotherapy are current standard treatment of CMM.3,4 The purpose of this case is to report our successful management of conjunctival melanoma using wide excision and cryotherapy.&#x0D; Case Illustration : A 67-year-old man who presented to our hospital with a large, pigmented lesion arising from inferior and superior fornix conjunctiva in his left eye since 6 months ago. On examination, a massive pigmented tumor sized 25 x 10 x 15 mm, protruding from inferior fornix conjunctiva and sized 7 x 5x 3 mm arising from superior fornix conjunctiva of left eye. The mass was excised with 3 mm free margin from the tumour border confirmed with negative frozen section and followed by cryotherapy and conjunctival reconstruction using oral mucous graft. Histopathology confirmed with invasive conjunctival melanoma arising in PAM with severe atypia and no lymphovascular and perineural metastasis&#x0D; Discussion : Two months after we performed wide excision, cryotherapy and oral mucous graft, no recurrence and conjunctival necrosis at primary site were reported.&#x0D; Conclusion : A local wide excision with ‘no touch technique’, cryotherapy and oral mucous graft confirmed with negative frozen section are the mainstay treatment of CMM and has achieved satisfying functional outcomes. Since the high recurrence rate of CMM, we have to close follow up for the next 3 years

Tumor-specific activation of folate receptor beta enables reprogramming of immune cells in the tumor microenvironment.

Folate receptors can perform folate transport, cell adhesion, and/or transcription factor functions. The beta isoform of the folate receptor (FRβ) has attracted considerable attention as a biomarker for immunosuppressive macrophages and myeloid-derived suppressor cells, however, its role in immunosuppression remains uncharacterized. We demonstrate here that FRβ cannot bind folate on healthy tissue macrophages, but does bind folate after macrophage incubation in anti-inflammatory cytokines or cancer cell-conditioned media. We further show that FRβ becomes functionally active following macrophage infiltration into solid tumors, and we exploit this tumor-induced activation to target a toll-like receptor 7 agonist specifically to immunosuppressive myeloid cells in solid tumors without altering myeloid cells in healthy tissues. We then use single-cell RNA-seq to characterize the changes in gene expression induced by the targeted repolarization of tumor-associated macrophages and finally show that their repolarization not only changes their own phenotype, but also induces a proinflammatory shift in all other immune cells of the same tumor mass, leading to potent suppression of tumor growth. Because this selective reprogramming of tumor myeloid cells is accompanied by no systemic toxicity, we propose that it should constitute a safe method to reprogram the tumor microenvironment.

Cyclooxygenase-2 (COX-2) Expression in Equine Melanocytic Tumors.

Equine melanocytic tumors are common and have an unusual benign behavior with low invasiveness and metastatic rates. However, tumoral mass growth is usually a concern that can have life-threatening consequences. COX-2 is related to oncogenesis, promoting neoplastic cell proliferation, invasion, and metastasis. The aim of this study was to evaluate the immunohistochemical expression of COX-2 in equine melanocytic tumors. Through extension and intensity of labeling, 39 melanocytomas and 38 melanomas were evaluated. Of the malignant tumors, 13.2% were negative and 63.2% presented a low COX-2 expression. Only 6 malignant tumors presented >50% of labeled cells, 18 malignant and 8 benign had an expression between 21 and 50%, 8 malignant and 3 benign tumors had an expression between 6 and 20%, 1 malignant tumor had an expression between 1 and 5%, and 5 malignant and 28 benign tumors had no expression. Malignant tumors showed higher COX-2 expression than did benign tumors, with statistically significant differences. The low levels of COX-2 may be one of the molecular reasons for the presence of expansive mass growth instead of the invasive pattern of other species, which is related to high COX-2 levels.

Prolactin-secreting pituitary adenomas: male-specific differences in pathogenesis, clinical presentation and treatment.

Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of PRLomas results from direct prolactin (PRL) action, duration and severity of hyperprolactinemia, and tumor mass effect. Male PRLomas, compared to females, tend to be larger and more invasive, are associated with higher PRL concentration at diagnosis, present higher proliferative potential, are more frequently resistant to standard pharmacotherapy, and thus may require multimodal approach, including surgical resection, radiotherapy, and alternative medical agents. Therefore, the management of PRLomas in men is challenging in many cases. Additionally, hyperprolactinemia is associated with a significant negative impact on men's health, including sexual function and fertility potential, bone health, cardiovascular and metabolic complications, leading to decreased quality of life. In this review, we highlight the differences in pathogenesis, clinical presentation and treatment of PRLomas concerning the male sex.

The effect of human umbilical cord mesenchymal stem cells conditioned medium combined with tamoxifen drug on BRCA1 and BRCA2 expression in breast cancer mouse models.

A growing number of studies has indicated that the expression of Breast Cancer Susceptibility Genes 1 (BRCA1) and BRCA2 contribute to the resistance to DNA-damaging chemotherapies. Tamoxifen induces tumor cell death by suppressing estrogen receptor (ER) signaling and inducing DNA damage, and BRCA1 upregulation causes Tamoxifen chemoresistance in breast cancer cells. Consequently, this research study aimed to investigate the possible therapeutic effect of Human Umbilical Cord Mesenchymal Stem Cells Conditioned Medium (UCMSCs-CM) on sensitizing breast cancer cells to Tamoxifen by regulating BRCA1 and BRCA2 expression in vivo. Forty female mice, 4-8 weeks old, with weight of 150g, were used for this study. Mouse 4T1 breast tumor models were established and then treated with UCMSCs-CM and Tamoxifen alone or in combination. After 10 days, the tumor masses were collected and the expression levels of BRCA1 and BRCA2 were evaluated using qRT-PCR assay. The results obtained from qRT-PCR assay illustrated that UCMSCs-CM, either alone or in combination with Tamoxifen, significantly downregulated the mRNA expression levels of BRCA1 in breast cancer mouse models. However, both UCMSCs-CM and Tamoxifen indicated no statistically significant impact on BRCA2 mRNA expression compared to controls. Our findings evidenced that UCMSCs-CM could be considered as a potential therapeutic option to modulate Tamoxifen chemosensitivity by regulating BRCA1 in breast cancer.

Should I stay or should I go? Transsulfuration influences invasion and growth in glioblastoma.

A major challenge in treating patients with glioblastoma is the inability to eliminate highly invasive cells with chemotherapy, radiation, or surgical resection. As cancer cells face the issue of replicating or invading neighboring tissue, they rewire their metabolism in a concerted effort to support necessary cellular processes and account for altered nutrient abundance. In this issue of the JCI, Garcia et al. compared an innovative 3D hydrogel-based invasion device to regional patient biopsies through a comprehensive multiomics-based approach paired with a CRISPR knockout screen. Their findings elucidate a role for cystathionine γ-lyase (CTH), an enzyme in the transsulfuration pathway, as a means of regulating the cellular response to oxidative stress. CTH-mediated conversion of cystathionine to cysteine was necessary for regulating reactive oxygen species to support invasion. Meanwhile, inhibition of CTH suppressed the invasive glioblastoma phenotype. However, inhibiting CTH resulted in a larger overall tumor mass. These findings suggest that targeting the transsulfuration pathway may serve as a means of redirecting glioblastoma to proliferate or invade.

A novel radiomics-miRNAs integrated model to predict the histopathology of residual retroperitoneal masses in metastatic nonseminomatous germ cell tumors.

A novel radiomics-miRNAs integrated model to predict the histopathology of residual retroperitoneal masses in metastatic nonseminomatous germ cell tumors.

Intra-adrenal Paraganglioma and Paraaortic Paraganglioma in 15 Years Old Boys

Intra-adrenal paraganglioma (also called pheochromocytoma) is a chromaffin cell tumor that arises in the adrenal medulla and produces excess catecholamines. Paraganglioma can also be located in the extra-adrenal area. The incidence rate of intra-adrenal and extra-adrenal paraganglioma is about 1 case per 2.500-6.500 population, highest incidence at 40-50 years old, and distribution is the same in males and females. Intra-adrenal paraganglioma in pediatrics is more familial, bilateral, multifocal, and malignant. In children, the incidence rate of these tumors was 8.86%, the ratio of boys to girls was 2:1, and the average age of 11. This article reports a case, of a 15 years old boy with severe headaches, recurrent seizures, and a hypertension crisis (143/103-220/110 mmHg). MSCT scan of abdominal showed solid mass heterogeneous with central necrotic multiple in the supero-anterior of the left and right kidneys and on the right anterolateral aorta as high as CV L2, impressive adrenal gland mass and extra-adrenal, suspect pheochromocytoma. Performed surgery, routine histopathological examination, and Immunohistochemistry. Macroscopic examination showed an oval round shape mass of left and right adrenal tumors as well as the paraaortic, a smooth outer surface of the capsular, with yellowish brown color mass tumor at cut surface, supple consistency. Microscopic examination showing adrenal gland and paraaortic tissue with fibrous capsule contains proliferation of neoplastic cells forming a nested alveolar (Zellballen) pattern with a round oval to polygonal cells, granular eosinophilic cytoplasm, round oval nuclei, surrounded by sustentacular cells. Chromogranin A and S-100 are positive. The case was concluded by clinical findings, histopathological, and immunohistochemistry as intra-adrenal paraganglioma and paraganglioma of paraaortic.

Severe coagulopathy and inflammation occurred after resection of giant right ventricular intimal sarcoma with cardiopulmonary bypass: a case report

BackgroundPrimary malignant cardiac tumors are rare in clinic, and surgical resection under cardiopulmonary bypass (CPB) remains the main treatment. The non-physiological perfusion process of CPB leads to contact activation, and the resulting coagulopathy and systemic inflammatory response syndrome (SIRS) are common complications. However, it is difficult to predict the impact of foreign tumor fragments on this pathophysiological process once they enter the bloodstream, making this phenomenon more complex and challenging.Case PresentationWe report a case of cardiac intimal sarcoma who developed severe coagulopathy and widespread inflammation after excision of massive right ventricular tumor and replacement of tricuspid valve by median sternotomy under CPB. Although the procedure was expected to cause tumor cell necrosis and precautions were taken, uncontrolled massive postoperative bleeding, persistent fever, abnormally elevated inflammatory markers, and recurrent malignant arrhythmias occurred after surgery. In addition to common factors, the most possible underlying mechanism is contact activation triggered following surgical procedure for intimal sarcoma with CPB.ConclusionPatients with intracardiac malignant tumors are at a high risk for serious contact activation during CPB. Preventive application of comprehensive anti-inflammatory measures such as drugs and adsorptive CPB technology, as well as point-of-care (POC) monitoring of coagulation status will be helpful for individualized guidance and optimization of CPB management, and improvement of patient prognosis.

Effect of Pioglitazone and Cetuximab on Colon Cancer Stem-like Cell (CCSLCs) Properties.

One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named "HT29-shE". In the present study, these cells were used to investigate the effect of pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents. The viability and IC50 rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring. The findings showed that Pio and Cet at concentrations of 250 μM and 40 μg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal-- to-epithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment. Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment.

Sphingomyelin synthase 2 promotes the stemness of breast cancer cells via modulating NF-κB signaling pathway

ObjectivesMulti-drug resistance (MDR) to chemotherapy is the main obstacle influencing the anti-tumor effect in breast cancer, which might lead to the metastasis and recurrence of cancer. Until now, there are still no effective methods that can overcome MDR. In this study, we aimed to investigate the role of sphingomyelin synthase 2 (SMS2) in breast cancer resistance.MethodsQuantitative RT-PCR analysis was performed to assess changes in mRNA expression. Western blot analysis was performed to detect protein expression. Inhibitory concentration value of adriamycin (ADR) was evaluated using CCK 8 assay. The stemness ability of breast cancer cells was assessed by spheroid-formation assay. Immunofluorescence staining was conducted to show the cellular distribution of proteins. Breast tumor masses were harvested from the xenograft tumor mouse model.ResultsSMS2 overexpression increased the IC50 values of breast cancer cells. SMS2 decreased the CD24 transcription level but increased the transcription levels of stemness-related genes including CD44, ALDH, OCT 4 and SOX2 in breast cancer cells. SMS2 overexpression promoted the nuclear translocation of phosphorylated NF-κB, while suppression of SMS2 could inhibit the NF-κB pathway.ConclusionsSMS2 increased the stemness of breast cancer cells via NF-κB signaling pathway, leading to resistance to the chemotherapeutic drug ADR. Thus, SMS2 might play a critical role in the development of breast cancer resistance, which is a previously unrecognized mechanism in breast cancer MDR development.

Aspectos quirúrgicos de un condrosarcoma en la cavidad nasal de un perro – Reporte de caso

Chondrosarcomas (CSA) are mesenchymal tumors characterized by the proliferation of cells and interstitial tissue, morphologically presenting cartilaginous features at different stages of development. Chondrosarcomas can be primary, originating from a previously normal bone, or secondary to a preexisting chondroma. They generally exhibit slow growth, low metastatic index, and are well-differentiated. Classified into two subtypes: myxoid (more frequent) and mesenchymal. In dogs, CSA accounts for approximately 10% of bone tumors. This report aims to describe a case of surgical treatment via rhinotomy in a dog with CSA in the nasal cavity, leading to a period of survival and quality of life for the patient. This case is reported based on the medical record data of a patient, treated in February of 2023 at a veterinary hospital in Juiz de Fora - MG. The canine patient, a female with no defined breed (NDB), 7 years and 2 months old, weighing 15.3 kg, presented dyspnea for a period of 1 year, as reported by the owner. Forty-five days before the medical appointment, intermittent right unilateral epistaxis began. The patient had previously received treatment for the same complaint, for which tranexamic acid and prednisolone were prescribed, resulting in temporary improvement. She was then referred for a computed tomography scan, which revealed a neoformation in the right nasal sinus. On March 2, 2023, the animal was admitted for surgical intervention, where the tumor mass was excised. After removing the content, the bed was washed with physiological saline at room temperature. For closure of the created cavity, a Waltex® polypropylene mesh was used, fixed at its edges to the musculature. The material collected from the right nasal cavity was sent for histopathological examination, which indicated that the neoformation was a Chondrosarcoma, with myxoid stroma and foci of mature chondroid differentiation. The surgical intervention proved to be effective and satisfactory, allowing the resection of the neoformation, later classified as chondrosarcoma, providing quality of life to the patient after the surgical procedure.

CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance.

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent subpopulations including a small fraction of cancer stem-like cells (CSCs) and non-cancer stem cells (non-CSCs) that make the most of the tumor mass. Like other CSCs, melanoma stem-like cells (MSCs) are characterized by their unique cell surface proteins/stemness markers and aberrant signaling pathways. In addition to its function as a robust marker for stemness properties, CD133 is crucial for the maintenance of stemness properties and drug resistance. Herein, the role of CD133-dependent activation of PI3K/mTOR in the regulation of melanoma progression, drug resistance, and recurrence is reviewed.

Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [169Yb]Yb2O3 nanoseeds.

Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [169Yb]Yb2O3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy. 169Yb (T½ = 32days) was produced by neutron irradiation of enriched (15.2% in 168Yb) Yb2O3 target in a nuclear reactor, radiochemically converted to [169Yb]YbCl3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb3+ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model. The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed. These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers.