Tumor Mass Research Articles

Breast Cancer Dormancy – Lessons Learnt

Despite early diagnosis and improved treatments, breast cancer remains a challenging disease. A strategic advantage for breast cancer recurrence is the ability of breast cancer cells to become quiescent and survive for decades in a dormant state within the endosteal region of the bone marrow. Breast cancer dormancy is triggered by exosome vesicles secreted by mesenchymal stem cells residing in the bone marrow. By mechanisms yet to be determined, dormant breast cancer cells are awakened leading to resurgence and metastasis. Experimental evidence supports the notion that dormant breast cancer cells are cancer stem cells recognized as tumor initiating and propagating cells with chemoresistant and metastatic properties. These cells represent less than 2% of the total tumor mass, which impose a significant barrier for their therapeutic targeting. This review focuses on cellular and molecular properties of breast cancer dormancy including tumor microenvironment, epigenetic regulation, cell signaling and metabolic reprogramming.

Manganese Ions Chelated Tumosomes as Autologous Cancer Nanovaccines for Effective Suppression of Postsurgical Tumor Relapse.

Autologous cancer vaccines represent a promising strategy to effectively suppress postoperative tumor relapse by eliciting tumor-specific immune responses that highly rely on the efficient internalization and lymph node-targeting delivery of vaccines. Herein, we report an autologous nanovaccine obtained by sequentially incorporating tumor plasma membrane proteins into liposomes, termed tumosomes, and chelating it with metallo-agonist of manganese ions. The yielded Mn-tumosomes with a positively charged surface exhibited significantly enhanced internalization by dendritic cells and enhanced lymph node targeting capacity, the latter of which is indicated by the near-infrared II fluorescence of silver sulfide nanoprobes labeled on their lipid bilayers. As a result, vaccination with Mn-tumosomes elicited potent tumor-specific CD8+ T cells to suppress the growth of challenged allogeneic tumors more effectively than vaccination via bolus injection of plain tumosomes and commercial immune agonists. Furthermore, with the excised tumor mass as the source of whole tumor cell antigens, the as-prepared autologous Mn-tumosomes effectively suppressed the growth of both residual tumor masses and spontaneously formed metastatic tumors, particularly in combination with anti-PD-1 immunotherapy. This work highlights a metal coordination based strategy to fabricate personalized whole-tumor cell nanovaccines with superior lymph node targeting and cellular uptake efficacy for the immunotherapeutic suppression of postoperative tumor relapse.

Temozolomide regulates primary central nerve system lymphoma, being resistant to high dose methotrexate-based chemotherapy and radiation

Introduction: Primary central nerve system lymphoma (PCNSL) is an intracranial malignancy. Combined chemotherapy with methotrexate, procarbazine, vincristine, and Rituximab, following radiation, sometimes results in partial response or progressive disease. Temozolomide (TMZ) administration has been proposed to salvage therapy. Case Report: A 72-year-old man had headache and forgetfulness. Mild disorientation was observed. Head magnetic resonance image revealed a mass lesion in the right frontal lobe. Pathological examination after an incisional biopsy revealed a diagnosis of diffuse large B cell lymphoma. Standard treatment consisted of 6 cycles of high-dose methotrexate-based chemotherapy with procarbazine and vincristine. Three cycles of high-dose methotrexate-based chemotherapy with procarbazine and vincristine, combined with Rituximab. Further, focal radiation therapy against core lesion with marginal area irradiation was performed. In spite of total standard treatment, the lesion was not under regulation. The patient continued TMZ therapy 29 cycles on an outpatient basis due to psychiatric complications that made it difficult to continue intravenous treatment in the hospital. The tumor mass and surrounding edematous lesions decreased. Conclusion: Oral TMZ administration was effective in an elderly patient with PCNSL, who had failed standard chemotherapy and radiation therapy. It was less invasive, allowed for transition to outpatient management, and provided adequate therapeutic benefit. Future indications for similar cases should be considered.

Leveraging the Immunological Impacts of Irreversible Electroporation as a New Frontier for Cancer Therapy.

Irreversible electroporation (IRE) is a nonthermally mediated tissue ablation modality that makes use of short pulsed electric fields to destroy cancerous lesions in situ. In the past two decades, IRE has established itself not only as an effective means to ablate small, unresectable tumor masses but also as a tool particularly qualified to modulate the tumor microenvironment in a way that dismantles pathways of cancer immunosuppression and permits the development of a systemic antitumor immune response. However, despite its immune-stimulating tendencies, for most cancers conventional IRE alone is insufficient to establish an immune response robust enough to fully eliminate disseminated disease and prevent recurrence. Here, we describe the current understanding of the histological and immunological effects of IRE, as well as recent efforts to optimize IRE parameters and develop rational combination therapies to increase the efficacy of the resulting immune response.

Metformin exerted tumoricidal effects on colon cancer tumoroids via the regulation of autophagy pathway

BackgroundDespite the existence of promising outcomes from standard 2D culture systems, these data are not completely akin to in vivo tumor parenchyma. Therefore, the development and fabrication of various 3D culture systems can in part mimic intricate cell-to-cell interaction within the real tumor mass. Here, we aimed to evaluate the tumoricidal impacts of metformin (MTF) on colorectal cancer (CRC) tumoroids in an in vitro system via the modulation of autophagy.MethodsCRC tumoroids were developed using human umbilical vein endothelial cells (HUVECs), adenocarcinoma HT29 cells, and fibroblasts (HFFF2) in a ratio of 1: 2: 1 and 2.5% methylcellulose. Tumoroids were exposed to different concentrations of MTF, ranging from 20 to 1000 mM, for 72 h. The survival rate was detected using an LDH release assay. The expression and protein levels of autophagy-related factors were measured using PCR array and western blotting, respectively. Using H & E, and immunofluorescence staining (Ki-67), the integrity and proliferation rate of CRC tumoroids were examined.ResultsThe current protocol yielded typical compact tumoroids with a dark central region. Despite slight changes in released LDH contents, no statistically significant differences were achieved in terms of cell toxicity in MTF-exposed groups compared to the control tumoroids, indicating the insufficiency of MTF in the induction of tumor cell death (p > 0.05). Western blotting indicated that the LC3II/I ratio was reduced in tumoroids exposed to 120 mM MTF (p < 0.05). These data coincided with the reduction of intracellular p62 content in MTF 120 mM-treated tumoroids compared to MTF 40 mM and control groups (p < 0.05). PCR array analysis confirmed the up-regulation, and down-regulation of several genes related to various signaling transduction pathways associated with autophagy machinery and shared effectors between autophagy and apoptosis in 40 and 120 mM MTF groups compared to the non-treated control group (p < 0.05). These changes were more prominent in tumoroids incubated with 120 mM MTF. Histological examination confirmed the loosening integrity of tumoroids in MTF-treated groups, especially 120 mM MTF, with the increase in cell death via the induction of apoptosis (chromatin marginalization) and necrotic (pyknotic nuclei) changes. In the 120 mM MTF group, spindle-shaped cells with the remnants of a fibrillar matrix were detected. Data indicated the reduction of proliferating Ki-67+ cells within the tumoroids by increasing the MTF concentration from 40 to 120 mM.ConclusionsDifferent shared autophagy/apoptosis genes were modulated in CRC tumoroids after MTF treatment coinciding with both typical necrotic and apoptotic cells within the tumoroid structure. MTF can inhibit the integrity and proliferation of CRC tumoroids in dose-dependent manner.

A multi-institutional retrospective study evaluating clinical outcomes and prognostic factors in patients with metastatic appendiceal adenocarcinoma.

69 Background: Appendiceal adenocarcinoma (AA), a rare cancer, has been reported to have high incidences of mucinous type histology, peritoneal metastasis, and relatively good prognosis. However, its chemotherapeutic efficacy and prognostic factors is not well known. Methods: We collected patients with metastatic AA treated with chemotherapy between February 2005 and March 2023 in two high volume cancer centers in Japan. We retrospectively analyzed the clinical outcomes of the chemotherapy of patients with metastatic AA and the clinical factors associated with treatment efficacy and prognosis by multivariate analysis. Results: A total of 66 patients with a median age of 54 years, were enrolled. 40 patients (60.6%) received an oxaliplatin-based regimen in combination with bevacizumab. The response rate was 22.0% and the disease control rate was 87.8%. With median follow-up period was 15.5 months [1.9-103.1], median progression-free survival (PFS) was 10.9 months [95% CI: 7.2-15.2] and median overall survival (OS) was 23.0 months [95% CI: 19.6-35.8]. 77.4% of patients received subsequent chemotherapy. In multivariate analysis, pretreatment carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9) were associated with significantly shorter PFS (HR: 2.93, P = 0.0049). Presence of primary tumor (HR:2.50, P = 0.015), ECOG performance status (PS) ≥1 (HR: 2.67, P = 0.0091), moderate to massive ascites (HR: 3.06, P = 0.0043) and high tumor marker levels (HR: 2.46, P = 0.026) were associated with significantly shorter OS. Classifying the patients by number of these prognostic factors for OS into three groups (0, 1-2, and 3-4), the group with prognostic factors (1-2 or 3-4) had a significantly shorter prognosis compared to the group without any these factors (0 vs 1-2: HR: 4.70, P = 0.038, 0 vs 3-4: HR: 17.6, P &lt; 0.01). In addition, the group with 3-4 prognostic factors had relatively lower rate of subsequent chemotherapy ratio than the group without these factors (66.7% vs 100%, P = 0.25). Conclusions: We confirmed our treatment outcomes were consistent with previous studies and elevation of tumor markers presence of primary tumor, ECOG PS ≥1, moderate to massive ascites were significantly associated with survival in patients with metastatic AA.

Tumor metastasis and recurrence: The role of perioperative NETosis.

Although surgical resection of tumor mass remains the mainstay of curative therapeutic management for solid tumors, accumulating studies suggest that these procedures promote tumor recurrence and metastasis. Regarded as the first immune cells to fight against infectious or inflammatory insults from surgery, neutrophils along with their ability of neutrophil extracellular traps (NETs) production has attracted much attention. A growing body of evidence suggests that NETs promote cancer metastasis by stimulating various stages, including local invasion, colonization, and growth. Therefore, we discussed the mechanism of NETosis induced by surgical stress and tumor cells, and the contribution of NETs on tumor metastasis: aid in the tumor cell migration and proliferation, evasion of immune surveillance, circulating tumor cell adhesion and establishment of a metastatic niche. Lastly, we summarized existing NET-targeting interventions, offering recent insights into potential targets for clinical intervention.

Design, synthesis and biological evaluation of novel β-carbolines as antitumor agents via targeting autophagy in colorectal cancer

A series of novel β-carbolines with a flexible amino side chain at positions 1 and 3, respectively, were designed, synthesized and evaluated as potential antitumor agents. The results revealed that most of the compounds exhibited a broad spectrum of antiproliferative activity with IC50 value lower than 20 μM against human tumor cell lines. Among them, compound 2f was the most potent antiproliferative agent with IC50 value below 5.0 μM against human tumor cell lines. Subsequent studies on the in vivo antitumor efficacy of the representative compound 2f demonstrated its ability to hinder tumor progression and significantly diminish tumor mass in a mouse model of colorectal cancer. Further investigation on mechanisms of action showed that compound 2f induced autophagy via the ATG5/ATG7 pathway in HCT116 cells. These compounds may contribute to the development of therapeutic agents for colorectal cancer.

Low-dose LPS and calorie restriction combined therapy for pancreatic ductal adenocarcinoma: an in vitro and in vivo study

Objective: This study aimed to evaluate the therapeutic effects of lipopolysaccharide (LPS) on Panc02 cells since LPS is an inflammatory agent with the potential to activate the immune system and reorganize the tumor microenvironment. Moreover, calorie restriction (CR) has been investigated in combination with LPS as a prospective adjuvant intervention for cancer therapy. Materials and Methods: Panc02 cells were cultured in two distinct media with low and high-glucose concentrations, and cell viability was investigated after applying varying doses of LPS to culture media. The in vivo effects of LPS and CR were investigated on the mice subcutaneous pancreatic ductal adenocarcinoma (PDAC) tumor model in terms of tumor mass, histological examination, mRNA expression profiles, and biochemical parameters. Results: The lowest cell count was detected in the cells treated with 10 μg/ml LPS in low-glucose environments in vivo. Tumor mass significantly decreased in the P+LPS+CR group in vivo. The mRNA expression analysis of tumor tissues indicated that P+LPS+CR acts through NF-κB, JNK, and IL-6 signaling pathways. Conclusion: Lipopolysaccharide alone is insufficient to show therapeutic effects, but it can inhibit tumor development by acting on NF-κB and JNK pathways when combined with CR. This study gives insight into developing new treatment options for PDAC.

Long-Term Outcomes in Radioiodine-Resistant Follicular Cell-Derived Thyroid Cancers Treated with [177Lu]Lu-DOTAGA.FAPi Dimer Therapy.

Aim: The study aimed to analyze the long-term outcomes of [177Lu]Lu-DOTAGA.FAPi dimer therapy in individuals diagnosed with radioiodine-resistant (RAI-R) follicular cell-derived thyroid cancer. Materials and Methods: In this retrospective study, 73 patients with RAI-R follicular thyroid carcinoma who had undergone multiple lines of previous treatments were included. Following [68Ga]Ga-DOTA.SA.FAPi positron emission tomography-computed tomography scan, among the 73 patients, 65 received [177Lu]Lu-DOTAGA.FAPi dimer monotherapy with a median activity of 5.5 GBq per cycle at 8-week intervals. The remaining eight patients underwent tandem [177Lu]Lu/[225Ac]Ac-DOTAGA.FAPi dimer therapy, consisting of a median of two cycles of [177Lu]Lu-DOTAGA.FAPi dimer followed by one cycle of [225Ac]Ac-DOTAGA.FAPi dimer, also at 8-week intervals. The primary endpoint included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included PERCIST criteria response assessment and safety assessment according to Common Terminology Criteria for Adverse Events (V5.0). Results: We enrolled 37 female and 36 male patients, with a mean age of 54.3 years (range: 27 - 80 years). The patients received a median cumulative activity of 22.2 GBq (range, 4 GBq-55.5 GBq) of [177Lu]Lu-DOTAGA-FAPi dimer over one to nine cycles, with a median of three cycles. Among 73 patients, 20 died and 16 deaths were due to thyroid cancer. Nineteen patients experienced disease progression, with an estimated median PFS of 29 months [CI 14-34 months]. The estimated median OS was 32 months [CI 21-40 months]. Four patients (5.4%) encountered grade III anemia, primarily linked to bone metastasis in three cases and neck tumor mass bleed in one. Grade III thrombocytopenia occurred in three patients (4%). No grade III renal or hepatotoxicity was observed. Conclusion: In this study, [177Lu]Lu-DOTAGA.FAPi dimer therapy showed promising safety and efficacy in aggressive, radioiodine-resistant thyroid cancer, achieving a median PFS and OS of 29 and 32 months, respectively, with manageable adverse events. Confirmation of our findings is needed from prospective clinical trials comparing [177Lu]Lu-DOTAGA.FAPi dimer therapy to other treatments.

Pulmonary Valve Fibroelastoma, Still a Very Rare Cardiac Tumor: Case Report and Literature Review

Background and Clinical Significance: Primary cardiac tumors are among the rarest types of tumor, and until the mid-20th century, they were diagnosed only post-mortem or during other surgical interventions. With the rapid evolution of cardiovascular imaging and the widespread use of echocardiography, the incidence of cardiac fibroelastoma has increased, though it remains one of the rarest primary cardiac tumors. Papillary fibroelastoma is a benign primary cardiac tumor that develops from endocardial tissue, is usually solitary, and can have multiple locations, with the pulmonary valve being one of the rarest sites. The symptoms and complications depend on the tumor’s location, ranging from asymptomatic patients to cerebral ischemic embolism or pulmonary embolism. We analyzed the electronic databases PubMed, Web of Science, and Cochrane and conducted a systematic review of pulmonary valve papillary fibroelastoma (PVPF). Additionally, we included a case from the Adult and Pediatric Cardiovascular Surgery Clinic in Targu Mures. Case Presentation: We present the case of a 58-year-old patient who complained of exertional dyspnea. A transthoracic echocardiography (TTE) revealed a tumor mass attached to the pulmonary valve and coronary angiography identified severe coronary lesions. Following discussions within the Heart Team, surgical myocardial revascularization and tumor excision were decided upon due to the thromboembolic risk. Histopathological examination confirmed the diagnosis of papillary fibroelastoma. The postoperative course was uneventful, with an improvement in dyspnea. The mean age of the patients was 60 years, with half being men (n = 26, 50%). Regarding symptoms, 34% (n = 18) of cases were incidentally identified, while over 30% (n = 17) presented with dyspnea. Pulmonary embolism (PE) was reported in only two patients, and the most common associated comorbidities included high blood pressure (HBP) in 33% (n = 16) and dyslipidemia in 18%. Tumor size ranged from 0.7 cm to 3 cm with the initial benign cardiac tumor; its occurrence in the pulmonary valve remains exceedingly rare. Due to its frequent overlap with other cardiac pathologies, the clinical presentation is often a nonspecific diagnosis or suspicion of a tumor predominantly established via transthoracic echocardiography in 62% of patients. From a surgical perspective, 63% (n = 33) underwent tumor resection with valve sparing, 25% (n = 12) required pulmonary valve repair, and three patients necessitated pulmonary valve replacement. Conclusions: Although the incidence of papillary fibroelastoma is increasing, making it the most common, there is a need to highlight the indispensable role of echocardiography in diagnosis. Although papillary fibroelastoma is benign, surgical intervention is recommended, particularly in symptomatic patients, or if the tumor exceeds 1 cm in size, exhibits increased mobility, or is present alongside other cardiac surgical procedures.

Genome-scale spatial mapping of the Hodgkin lymphoma microenvironment identifies tumor cell survival factors.

A key challenge in cancer research is to identify the secreted factors that contribute to tumor cell survival. Nowhere is this more evident than in Hodgkin lymphoma, where malignant Hodgkin Reed Sternberg (HRS) cells comprise only 1-5% of the tumor mass, the remainder being infiltrating immune cells that presumably are required for the survival of the HRS cells. Until now, there has been no way to characterize the complex Hodgkin lymphoma tumor microenvironment at genome scale. Here, we performed genome-wide transcriptional profiling with spatial and single-cell resolution. We show that the neighborhood surrounding HRS cells forms a distinct niche involving 31 immune and stromal cell types and is enriched in CD4+ T cells, myeloid and follicular dendritic cells, while being depleted of plasma cells. Moreover, we used machine learning to nominate ligand-receptor pairs enriched in the HRS cell niche. Specifically, we identified IL13 as a candidate survival factor. In support of this hypothesis, recombinant IL13 augmented the proliferation of HRS cells in vitro . In addition, genome-wide CRISPR/Cas9 loss-of-function studies across more than 1,000 human cancer cell lines showed that IL4R and IL13RA1, the heterodimeric partners that constitute the IL13 receptor, were uniquely required for the survival of HRS cells. Moreover, monoclonal antibodies targeting either IL4R or IL13R phenocopied the genetic loss of function studies. IL13-targeting antibodies are already FDA-approved for atopic dermatitis, suggesting that clinical trials testing such agents should be explored in patients with Hodgkin lymphoma.

Genes and proteins expression profile of 2D vs 3D cancer models: a comparative analysis for better tumor insights.

When juxtaposed with 2D cell culture models, multicellular tumor spheroids demonstrate a capacity to faithfully replicate certain features inherent to solid tumors. These include spatial architecture, physiological responses, the release of soluble mediators, patterns of gene expression, and mechanisms of drug resistance. The morphological and behavioural similarities between 3D-cultured cells and cells within tumor masses highlight the potential of these models in studying cancer biology and drug responses. The liquid overlay method, hanging drop technique, and ultra-low adhesion plates are among the various methods for generating tumor spheroids, each with its advantages and applications. Gene expression studies, employing advanced methods such as microarrays, suppression subtractive hybridization, qRT-PCR, and mass-spectrometry-based proteomics revealed distinct expression patterns in 3D spheroids compared to 2D cultures, uncovering upregulation and downregulation of genes associated with tumor development, metastasis, and drug resistance. Protein expression studies identified alterations in key signaling pathways, metabolic characteristics, and phosphorylation levels, highlighting the impact of 3D culture on cellular responses. This study explores genes and proteins expression variations in various cancer cell lines cultivated in 3D spheroids, shedding light on the complexity of interactions in a more tumor-mimicking environment. The fusion of these analytical approaches not only advances scientific understanding but also holds promise for the development of more effective cancer treatments.

A punção aspirativa por agulha fina como ferramenta diagnóstica de tumor de células melanocíticas em cavalo tordilho

Melanocytic cell tumors, commonly known as melanomas, are frequently observed in grey horses, especially in older animals. These tumors can range from benign to malignant and are often diagnosed in areas such as the base of the tail, perineum, lips, and parotid glands. Fine-Needle Aspiration (FNA) has proven to be a valuable diagnostic tool in the evaluation of neoplasms, allowing for the collection of tumor cells for cytological analysis in a minimally invasive and cost-effective manner for many owners. This case report describes the use of FNA in diagnosing a benign melanocytic tumor in a 15-year-old grey horse that presented a subcutaneous mass in the submandibular region, as well as formations at the base of the tail and lips. After collecting the material via FNA, the samples were subjected to cytological analysis, where no malignancy criteria were observed. Since surgical intervention and histopathological evaluation were not opted for, treatment with Cimetidine was initiated to reduce the tumor masses. The application of FNA proved to be an efficient and practical technique in obtaining diagnostic material, allowing for early tumor identification and aiding in the clinical management of the patient. This report reinforces the importance of FNA as a diagnostic tool in veterinary medicine, especially in cases of cutaneous neoplasms in horses, where quick and accurate interventions are essential for successful treatment.

HVEM as a Tumor-Intrinsic Regulator in Non-Small Cell Lung Cancer: Suppression of Metastasis via Glycolysis Inhibition and Modulation of Macrophage Polarization.

Herpes virus entry mediator (HVEM) is a novel costimulatory molecule which mediates stimulatory or inhibitory signals in immune responses which makes it an attractive target in cancer therapeutics. However, the role of tumor cell intrinsic HVEM on tumor biology remains largely unknown. In this study, We demonstrated that CK+HVEM+ tumor correlates with better survival using Multiplex immuno histochemistry (mIHC) in Human Lung Adenocarcinoma Tissue microarray. Next, we showed that HVEM knockdown promoted NSCLC cell invasion and metastasis in vitro whereas exhibited no effect on proliferation. Conversely, HVEM overexpression results in the opposite phenotype. Meanwhile, the conclusion were further confirmed in vivo experiment that overexpression of HVEM reduced the invasion and metastasis of NSCLC whereas no effect on tumor mass. Besides, vivo experiment showed that M1 TAMs in the HVEM overxrpression group was increased and the proportion of M2 macrophages was decreased compared to the vector group. Mechanistically, The C-terminal 228-283 amino acid segment of HVEM protein interacts with the N-terminal 1-383 amino acid segment of MPRIP protein, inhibiting its downstream glycolysis signaling pathway and suppressing NSCLC cells progression. In addition, macrophage coculture assay suggested that HVEM overexpression inhibited M2 macrophage polarization through GM-CSF/GM-CSFRα axis. In summary, our study has demonstrated that tumor cell intrinsic HVEM is a potential tumour metastasis suppressor, which may serve as a potential target for immunotherapy.

Transforming bacterial pathogens into wonder tools in cancer immunotherapy.

Cancer immunotherapy has revolutionized cancer treatment due to its precise, target-specific approach compared with conventional therapies. However, treating solid tumors remains challenging as these tumors are inherently immunosuppressive, and their tumor microenvironment (TME) often limits therapeutic efficacy. Interestingly, certain bacterial species offer a promising alternative by exhibiting an innate ability to target and proliferate within tumor environments. Bacterial structural and functional components can activate innate and adaptive immune responses, creating tumor-suppressive conditions that reduce tumor mass. Additionally, bacteria can deliver effector molecules directly into tumor cells, inducing apoptotic and necrotic cell death. Despite their potential, the use of bacteria in cancer immunotherapy poses risks due to possible toxicities and unpredictable invivo behavior. Advances in genetic engineering have addressed these concerns by enabling the development of attenuated bacterial strains with enhanced anticancer properties for safer medical applications. This review highlights the role of bacteria in TME modulation, recent strategies to bioengineer bacterial pathogens as therapeutic tools, and the synergistic effects of combining bacteria with other immunotherapies. It also discusses the challenges and prospects of translating this innovative approach into clinical practice, offering a comprehensive overview of bacteria-based cancer immunotherapy's potential to reshape the future of cancer treatment.

KRT20-/SATB2+/MCPyV+ Sinonasal Merkel Cell Carcinoma: A Detailed Immunohistochemical and In Situ Hybridization Study.

Merkel cell carcinoma (MCC) is an uncommon aggressive neoplasm, usually arising in sun-exposed skin of the head and neck. By immunohistochemistry, KRT20 and MCPyV positivity are found in about 90% and 80% of MCCs, respectively. Noteworthy, viral status in lip/oral cavity MCCs is poorly known. A 78-year-old male was referred presenting a tumor mass on the right maxilla four months ago. Computed tomography revealed an extensive osteolytic lesion in the right maxillary sinus extending into the orbit and nasal cavity and crossing the midline. Microscopy revealed large necrotic areas admixed by sheets of small, round cells with hyperchromatic nuclei exhibiting a '"salt and pepper" chromatin pattern, which showed immunopositivity for pan-KRT AE1/AE3, EMA, CD56, CD99 (weak), CD138, S100 (focal), vimentin (focal), synaptophysin, FLI1, INSM1, MCPyV, SATB2, and Ki-67 (MKI67 [40%]). Moreover, intact RB1 and wild-type p53 expression were observed. Relevantly, KRT20, KRT5/6, chromogranin A, p40, p63, HMB45, NF, TTF1, TDT (DNTT), PAX5, p16, KIT, as well as high-risk HPV and EBER1/2 (both by ISH), were negative. This report illustrates that a detailed immunohistochemical study, including STAB2 and MCPyV markers, as well as a careful clinical workup, are essential to adequately classify high-grade neuroendocrine carcinomas, especially KRT20-negative MCC.

A Rare Case of Neonatal Desmoid Tumor Leading to Severe Aortic Coarctation: Review of Literature and Case Report.

Desmoid tumors are a rare entity, especially in the pediatric population. There are no reports of such a tumor in newborns. They are associated with high rates of morbidity and mortality, even though they are benign soft tissue tumors. This is due to them exhibiting locally aggressive growth with the compression or invasion of adjacent structures. Abdominal localization is most commonly reported, although there are reports of mediastinal desmoid tumors. We present the case of a 6-day male patient with a mediastinal desmoid tumor that led to severe aortic coarctation with hemodynamic instability. The tumor also compressed the left pulmonary artery and obstructed the left main bronchus. The initial management consisted of successful emergency surgery with partial resection of the tumor mass and coarctation repair. In the postoperative setting, the patient evolved with severe respiratory dysfunction which was managed with tracheostomy, allowing weaning the child from the mechanical ventilation one month after surgery, along with chemotherapy. We also review the literature, focusing on the management of desmoid tumors.

Idarubicin-loaded chitosan nanobubbles to improve survival and decrease drug side effects in hepatocellular carcinoma.

Drug delivery strategies using chitosan nanobubbles (CS-NBs) could be used to reduce drug side effects and improve outcomes in hepatocellular carcinoma (HCC) treatment. To enhance their action, a targeting agent, such as the humanized anti-GPC3 antibody GC33 (condrituzumab), could be attached to their surface. Here, we investigated the use of idarubicin-loaded CS-NBs for HCC treatment and a GC33-derived minibody (that we named 4A1) to enhance CS-NB delivery. Various CS-NB formulations were prepared with or without 4A1 conjugation and idarubicin loading. CS-NBs had a positive charge and a diameter of about 360 nm. In in-vitro experiments using the HCC-like HUH7 cell line, CS-NBs showed a cytotoxic effect once loaded with idarubicin. In-vivo biodistribution in HUH7 tumor-bearing xenograft mice demonstrated that CS-NBs can accumulate in the tumor mass. This effect was enhanced by 4A1 conjugation (p = 0.0317). In HUH7 tumor-bearing xenograft mice, CS-NBs loaded with idarubicin and conjugated or not conjugated with 4A1 were both able to slow tumor growth, to increase mouse survival time compared to free idarubicin (p = 0.00044 and 0.0018, respectively) as well as to reduce drug side effects. CS-NBs loaded with idarubicin can be a useful drug delivery strategy for HCC treatment.

Conventional Chemotherapy and Inflammation: What Is the Role of the Inflammasome in the Tumor Microenvironment?

The link between inflammation and cancer has been extensively studied over the years. While the inflammatory process can facilitate tumor establishment and progression, on the other hand, current clinical approaches aim to boost the immune system against the tumor mass. In this scenario, the conventional chemotherapy has proven to induce immunogenic cell death in that the release of danger-associated alarmins can foster the cytotoxic immunity following the blockade of immune checkpoints. The release of alarmins can activate the inflammasome pathway. Thus, one of the questions is as follows: can conventional anti-tumor drugs lead to inflammasome activation? And if so, is the resulting effect anti- or pro-tumor? In this review, we provide an overview on the role of the inflammasome in cancer.