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BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Background: Anticancer treatments aim to selectively target cancer cells without harming normal cells. While non-thermal atmospheric pressure plasma (NTAPP) has shown anticancer potential across various studies, the mechanisms behind its selective action on cancer cells remain inadequately understood. This study explores the mechanism of NTAPP-induced selective cell death and assesses its application in cancer therapy. Methods: We treated HT1080 fibrosarcoma cells with NTAPP and assessed the intracellular levels of mitochondria-derived reactive oxygen species (ROS), mitochondrial function, and cell death mechanisms. We employed N-acetylcysteine to investigate ROS's role in NTAPP-induced cell death. Additionally, single-cell RNA sequencing was used to compare gene expression in NTAPP-treated HT1080 cells and human normal fibroblasts (NF). Western blotting and immunofluorescence staining examined the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), a key antioxidant gene transcription factor. We also evaluated autophagy activity through fluorescence staining and transmission electron microscopy. Results: NTAPP treatment increased ROS levels and induced mitochondrial dysfunction, leading to apoptosis in HT1080 cells. The involvement of ROS in selective cancer cell death was confirmed by N-acetylcysteine treatment. Distinct gene expression patterns were observed between NTAPP-treated NF and HT1080 cells, with NF showing upregulated antioxidant gene expression. Notably, NRF2 expression and nuclear translocation increased in NF but not in HT1080 cells. Furthermore, autophagy activity was significantly higher in normal cells compared to cancer cells. Conclusions: Our study demonstrates that NTAPP induces selective cell death in fibrosarcoma cells through the downregulation of the NRF2-induced ROS scavenger system and inhibition of autophagy. These findings suggest NTAPP's potential as a cancer therapy that minimizes damage to normal cells while effectively targeting cancer cells. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that B-subgroup rapidly accelerated fibrosarcoma (RAF) kinases have pivotal roles in hormone signaling and stress responses across a wide range of organisms. In this forum, I explore their evolution and diverse signaling pathways, highlighting the significance of B-RAF kinases in plant growth and plant–environment interactions while discussing open questions for future research. [ABSTRACT FROM AUTHOR]

Abstract Background Anticancer treatments aim to selectively target cancer cells without harming normal cells. While non-thermal atmospheric pressure plasma (NTAPP) has shown anticancer potential across various studies, the mechanisms behind its selective action on cancer cells remain inadequately understood. This study explores the mechanism of NTAPP-induced selective cell death and assesses its application in cancer therapy. Methods We treated HT1080 fibrosarcoma cells with NTAPP and assessed the intracellular levels of mitochondria-derived reactive oxygen species (ROS), mitochondrial function, and cell death mechanisms. We employed N-acetylcysteine to investigate ROS’s role in NTAPP-induced cell death. Additionally, single-cell RNA sequencing was used to compare gene expression in NTAPP-treated HT1080 cells and human normal fibroblasts (NF). Western blotting and immunofluorescence staining examined the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), a key antioxidant gene transcription factor. We also evaluated autophagy activity through fluorescence staining and transmission electron microscopy. Results NTAPP treatment increased ROS levels and induced mitochondrial dysfunction, leading to apoptosis in HT1080 cells. The involvement of ROS in selective cancer cell death was confirmed by N-acetylcysteine treatment. Distinct gene expression patterns were observed between NTAPP-treated NF and HT1080 cells, with NF showing upregulated antioxidant gene expression. Notably, NRF2 expression and nuclear translocation increased in NF but not in HT1080 cells. Furthermore, autophagy activity was significantly higher in normal cells compared to cancer cells. Conclusions Our study demonstrates that NTAPP induces selective cell death in fibrosarcoma cells through the downregulation of the NRF2-induced ROS scavenger system and inhibition of autophagy. These findings suggest NTAPP’s potential as a cancer therapy that minimizes damage to normal cells while effectively targeting cancer cells.

For many cancer patients tumor burden negatively impacts quality of life due to associated pain onset. Neuropathic pain is commonly associated with late cancer stages, and is resultant of tumor metastasis to bone, herein referred to as cancer-induced bone pain. Given the severe impact on quality of life and clinical treatment strategies focusing on symptom management, novel therapeutics are needed to alleviate cancer-induced bone pain and/or reduce cancer burden. In the current study we characterized a commercially available murine fibrosarcoma cell line, NCTC-2472 in vitro, which can be used to assess the capacity of novel compounds to impact cellular viability. We found that dimethyl sulfoxide, a known cytotoxic agent and common drug preparation compound, significantly decreased cell viability in a dose-related manner. We then characterized the in vivo tumor development and associated pain behavior characteristics following implantation of NCTC-2472 fibrosarcoma into male and female C3H/HeJ mice. The C3H/HeJ strain was utilized as these mice are syngeneic with NCTC-2472 fibrosarcoma and their use reduces potential implantation failure. We found that tumor development in mice resulted in the development of mechanical allodynia but not thermal hyperalgesia. Gabapentin, a clinically relevant analgesic, produced dose-related mechanical allodynia reversal. These studies provide further characterization of a cancer-induced bone pain model that can be used to examine novel compounds as anti-cancer and analgesic therapeutics. [ABSTRACT FROM AUTHOR]

Neoplasms in small ruminants are considered uncommon and their reported incidence is variable. The aims of this investigation were to characterize malignant skin neoplasms in adult goats reared in Sicily, Italy, and to evaluate potential correlations between gross and histopathology features of the tumours and signalment, tumour location and/or viral infections. A total of 75 malignant skin masses were examined. In selected animals with perineal masses (n = 28) virological and serological investigations on tissues and blood were also conducted. According to the histological features, the lesions were classified as 67 squamous cell carcinomas (SCCs) (of which 65 were located in the perineum), six melanomas and two fibrosarcomas. In three cases, neoplasms at the base of the horn were associated with nasal polyps. Among the selected perineal SCCs, papillomaviruses (PVs), caprine herpesvirus 1 and parapoxvirus were not detected on polymerase chain reaction or on serological examination. However, further investigation on a larger sample size is required to evaluate the potential role of PVs in the pathogenesis of skin tumours in goats. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: The aim of our research was to assess the expression of the selected proteins involved with inflammation and carcinogenesis, in order to expand knowledge of FISS and non-FISS. Matrix metalloproteinase-2, matrix metalloproteinase-9, cyclooxygenase-2, and P-glycoprotein were evaluated with the immunohistochemistry method. Our results showed that the expressions of COX-2, MMP-9, and PGP were significantly higher in FISS than in non-FISS Feline injection-site sarcomas (FISSs) are aggressive neoplasms that have been associated mostly with vaccination. Feline noninjection-site sarcomas (non-FISSs) are less frequently observed in cats and may arise in any anatomic site. This study aimed to determine the differences in the expression of the selected proteins (matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and P-glycoprotein (PGP)) and their correlation with the mitotic count in FISS and non-FISS, in order to characterize their immunohistochemical features. A preliminary study of eleven samples of FISS and eight samples of non-FISS was performed using immunohistochemistry. Among all the tested sarcomas, 80.4% of the tumors were positive for COX-2, 90.2% were positive for MMP-9, and 100% were positive for PGP. The results showed that the expressions of COX-2, MMP-9, and PGP were significantly higher in FISS than in non-FISS (COX-2—p ≤ 0.001; MMP-9—p ≤ 0.05; and PGP—p ≤ 0.05). A Spearman rank correlation analysis showed a moderate negative correlation between the expression of COX-2 and MMP-9 in FISS (r = −0.52). A strong negative correlation between COX-2 and PGP (r = −0.81), a moderate positive correlation between MMP-2 and MMP-9 (r = +0.69), and a moderate negative correlation between MMP-2 and PGP (r = −0.44) were observed in non-FISS. In summary, our study presents the immunohistochemical profile of the proteins involved with inflammation and carcinogenesis in FISS and non-FISS, which can contribute to expanding the knowledge of tumor biology. [ABSTRACT FROM AUTHOR]

The diagnosis or rare mesenchymal malignant lesions of the liver may be a challenge owing to the rarity of the disease and is usually made by histological confirmation. An ultrasound examination with, if required, color Doppler sonography and contrast-enhanced ultrasound, taking into account the clinical background of the patient, may help to focus the differential diagnosis. In this review, we describe the pathological and ultrasound features of several rare mesenchymal malignant liver lesions which include undifferentiated sarcoma of the liver, leiomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, and epithelioid hemangioendothelioma. [ABSTRACT FROM AUTHOR]

A 9‐year‐old, female spayed domestic short‐haired cat was presented with a 4‐year history of bilateral lipogranulomatous conjunctivitis (LGC), which was confirmed via histopathology. Thirteen months following the initial biopsy, the cat was presented with a rapidly progressive mass lesion of the palpebral conjunctiva of the right eye. A surgical debulking, followed 1 month later by exenteration after marked regrowth of the mass confirmed fibrosarcoma. This case report is the first to describe a cat with chronic bilateral LGC that later developed a unilateral fibrosarcoma within the eyelid tissue of the right eye. Fibrosarcoma should be considered a differential in any cat with chronic LGC that develops a rapidly progressive mass in the eyelid. [ABSTRACT FROM AUTHOR]

This study demonstrated the anticancer efficacy of chalcones with indole moiety (MIPP, MOMIPP) in fibrosarcoma cells for the first time. The results showed that MIPP and MOMIPP reduced the viability of HT-1080 cells in a concentration-dependent manner. MOMIPP was more active than MIPP in HT-1080 cells, showing lower IC50 values (3.67 vs. 29.90 μM). Both compounds at a concentration of 1 μM induced apoptosis in HT-1080 cells, causing death strictly related to caspase activation, as cell viability was restored when the caspase inhibitor Z-VAD was added. Reactive oxygen species production was approximately 3-fold higher than in control cells, and cotreatment with the inhibitor of mitochondrial ATPase oligomycin diminished this effect. Such effects were also reflected in mitochondrial dysfunction, including decreased membrane potential. Interestingly, the compounds that were studied caused massive vacuolization in HT-1080 cells. Immunocytochemical staining and TEM analysis showed that HT-1080 cells exhibited increased expression of the LC3-II protein and the presence of autophagosomes with a double membrane, respectively. Both compounds induced apoptosis, highlighting a promising link between autophagy and apoptosis. This connection could be a new target for therapeutic strategies to overcome chemoresistance, which is a significant cause of treatment failure and tumour recurrence in fibrosarcoma following traditional chemotherapy. [ABSTRACT FROM AUTHOR]

Ionizing radiation (IR) can reprogram proteasome structure and function in cells and tissues. In this article, we show that IR can promote immunoproteasome synthesis with important implications for Ag processing and presentation and tumor immunity. Irradiation of a murine fibrosarcoma (FSA) induced dose-dependent de novo biosynthesis of the immunoproteasome subunits LMP7, LMP2, and Mecl-1, in concert with other changes in the Ag-presentation machinery (APM) essential for CD8+ T cell-mediated immunity, including enhanced expression of MHC class I (MHC-I), β2-microglobulin, transporters associated with Ag processing molecules, and their key transcriptional activator NOD-like receptor family CARD domain containing 5. In contrast, in another less immunogenic, murine fibrosarcoma (NFSA), LMP7 transcripts and expression of components of the immunoproteasome and the APM were muted after IR, which affected MHC-I expression and CD8+ T lymphocyte infiltration into NFSA tumors in vivo. Introduction of LMP7 into NFSA largely corrected these deficiencies, enhancing MHC-I expression and in vivo tumor immunogenicity. The immune adaptation in response to IR mirrored many aspects of the response to IFN-γ in coordinating the transcriptional MHC-I program, albeit with notable differences. Further investigations showed divergent upstream pathways in that, unlike IFN-γ, IR failed to activate STAT-1 in either FSA or NFSA cells while heavily relying on NF-κB activation. The IR-induced shift toward immunoproteasome production within a tumor indicates that proteasomal reprogramming is part of an integrated and dynamic tumor-host response that is specific to the stressor and the tumor and therefore is of clinical relevance for radiation oncology.

This article discusses a rare and diagnostically challenging soft-tissue tumor called myxoid "pauci-hemosiderotic" fibrolipomatous tumor (HFLT). HFLT is characterized by an admixture of CD34-positive spindle cells, mature adipocytes, and hemosiderin-laden macrophages. It typically occurs in the subcutis of the distal lower extremities and has a local recurrence rate of up to 50%. Cytogenetic studies have identified translocations involving the TGFBR3 and OGA genes in most HFLT cases. The article presents a case study of a 38-year-old transgender male with a myxoid pHFLT tumor and highlights the challenges in diagnosing this rare entity. [Extracted from the article]

Solid organ transplant patients are at an increased risk of developing various types of malignancies. Herein, we have reported the case of a 32-year-old male patient, who presented with a nodular mass in the left shoulder 4 months after undergoing deceased donor renal transplantation. Local excision and biopsy were performed which revealed a malignant spindle cell tumor. Immunohistochemistry revealed S100 faint nuclear positivity in a few cells, CD34 positive, Ki67 1% low, and SMA negative suggestive of low-grade fibroblastic origin spindle cell tumor. This is a rare low-grade sarcoma with a high rate of local recurrence, rarely leading to amputation. Metastasis to the lungs and liver has been seldom reported. Our patient had local recurrence twice posttransplant for which he underwent wide local excision.

Ovarian fibrosarcomas account for less than 1% of all ovarian malignancies. Clinical diagnosis is extremely difficult. A 20-year-old, illiterate, married nulliparous woman presented to our Outpatient Department Clinic (OPD) with chronic abdominal distension. Ultrasound and CT scan revealed a very large intra-abdominal mass, 23.8x27.8x35.7cm. She underwent a laparotomy and left salpingo-oophorectomy with her uterus and right adenexum conserved. After surgery, the mass weighed 11.1kg and measured 43x38x35cm. Histological findings were in line with a giant primary ovarian fibrosarcoma. To date, as far as we are aware, this is the largest ever recorded primary ovarian fibrosarcoma.

Sclerosing epithelioid fibrosarcoma is a rare fibrosarcoma variant in which more than half of patients experience local recurrence or metastatic spread. In the current literature, there is limited and nonspecific imaging data, contributing to frequent misdiagnosis and delays in treatment intervention. Given the poor prognosis associated with this malignancy and the high probability of metastases, accurate and prompt diagnoses are critical. In this article, we report the case of a 27-year-old female diagnosed with metastatic sclerosing epithelioid fibrosarcoma following the discovery of a growing palpable mass on her right gluteus maximus muscle. We focus on the use of radiological imaging modalities in optimizing diagnosis and correlate our imaging and pathological findings.

Juvenile fibrosarcoma (JFS) is a rare case that accounts for only 1% of all pediatric tumors, which are aggressive and fast-growing. Most arises in the distal extremities than any other parts. This case report presents the case of a 2-year-old girl with complaints of right nasal obstruction. The initial clinical impression was an antrochoanal polyp, which was further supported by radiology. Histopathology showed the appearance of rhabdomyosarcoma. After evaluation, the patient underwent endoscopic endonasal surgery (EES). However, immunohistochemistry shows positive vimentin and Ki67 that lead to the diagnosis of JFS. Six months post-EES, the evaluation showed an impression of recurrence, so revision surgery was planned. After revision, histopathology showed no tumor tissue. This case highlights the diagnosis and management in JFS, emphasizing the importance of close monitoring and follow-up. This report contributes to the understanding and management of JFS, providing insights into diagnosis and treatment strategies.

Pleomorphic dermal sarcomas are infrequent neoplastic skin tumors, manifesting in regions of the skin exposed to ultraviolet radiation. Diagnosing the entity can be challenging and therapeutic options are limited. We analyzed 20 samples of normal healthy skin tissue (SNT), 27 malignant melanomas (MM), 20 cutaneous squamous cell carcinomas (cSCC), and 24 pleomorphic dermal sarcomas (PDS) using mass spectrometry. We explored a potential cell of origin in PDS and validated our findings using publicly available single-cell sequencing data. By correlating tumor purity (TP), inferred by both RNA- and DNA-sequencing, to protein abundance, we found that fibroblasts shared most of the proteins correlating to TP. This observation could also be made using publicly available SNT single cell sequencing data. Moreover, we studied relevant pathways of receptor/ligand (R/L) interactions. Analysis of R/L interactions revealed distinct pathways in cSCC, MM and PDS, with a prominent role of PDGFRB-PDGFD R/L interactions and upregulation of PI3K/AKT signaling pathway. By studying differentially expressed proteins between cSCC and PDS, markers such as MAP1B could differentiate between these two entities. To this end, we studied proteins associated with immunosuppression in PDS, uncovering that immunologically cold PDS cases shared a "negative regulation of interferon-gamma signaling" according to overrepresentation analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated a new imaging technique called ex vivo confocal microscopy to examine rare skin conditions. By analyzing tissue samples from different skin disorders, we found that this technique could accurately identify unique microscopic features of both common and rare skin diseases. Importantly, examiners with more experience in interpreting these images achieved higher accuracy in diagnosis. This suggests that ex vivo confocal microscopy has the potential to be a valuable tool alongside traditional methods for diagnosing rare skin conditions early and accurately, leading to better treatment outcomes for patients. While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some rare skin tumors as well as a few inflammatory skin diseases, that have not yet been studied in ex vivo confocal laser scanning microscopy. A total of 50 tissue samples comprising 10 healthy controls, 10 basal cell carcinoma, 10 squamous cell carcinoma, and 20 rare skin conditions were imaged using the newest generation ex vivo confocal microscopy (Vivascope 2500 M-G4, Vivascope GmbH, Munich, Germany). Three blinded investigators were asked to identify characteristic features of rare skin disorders and distinguish them from more common skin diseases in the ex vivo confocal microscopy images. Our findings present the capability of ex vivo confocal microscopy to display distinctive morphologic patterns in common and rare skin diseases. As might be expected, we found a strong correlation between imaging experience and diagnostic accuracy. While the imaging inexperienced dermatohistopathologist reached 60% concordance, the imaging-trained dermatologist obtained 88% agreement with dermatohistopathology. The imaging-trained dermatohistopathologist achieved concordance up to 92% with gold-standard dermatohistopathology. This study highlights the potential of ex vivo confocal laser scanning microscopy as a promising adjunct to conventional dermatohistopathology for the early and precise identification of rare dermatological disorders. [ABSTRACT FROM AUTHOR]

Thyroid fibrosarcomas represent a rare subset of tumors with exceedingly limited documented cases in the medical literature. This study delineates an unusual occurrence involving a 32-year-old female presenting with symptoms including neck pain, dysphagia, and dyspnea. Notably, the patient experienced symptom recurrence 3 months postthyroidectomy, accompanied by aggressive tumor growth. Despite the considerable size of the tumor and its infiltration into critical anatomical structures, a complex surgical intervention was executed with successful outcomes. The study underscores the imperative for further exploration into the efficacy of proposed therapeutic modalities tailored for managing this neoplasm. Moreover, it emphasizes the necessity for considering the histological classification of fibrosarcoma within the differential diagnoses spectrum for thyroid tumors. [ABSTRACT FROM AUTHOR]

The aim was to detect and correlate anticancer effects of metformin in combinations with other repurposed drugs, already registered for other indications, which may be immediately applied and clinically investigated in oncology, reducing the time and cost of research for new cancer treatments. Immunohistochemistry was performed for tumors treated by dual drug combinations containing metformin with deoxycholic acid, caffeine, itraconazole, nitroglycerin, disulfiram or diclofenac. The drugs were applied in Syrian golden hamsters (6 animals per group) with the inoculated BHK21/C13 fibrosarcoma in doses equivalent to usual human doses, <50 % LD50. The anticancer effects were assessed by: p53 (mutational status); Ki-67 and PCNA (tumor proliferation); CD34 and CD31 (neoangiogenesis); GLUT1 (glucose metabolism); iNOS (NO metabolism); COX4, Cytochrome C and caspase 3 (apoptosis); immunohistochemical markers. Also, biophysical characteristics of fibrosarcoma, animal blood samples and the toxicity on main organs were analyzed. Treatments significantly (P < 0.05) reduced mutational status, tumor proliferation, neoangiogenesis, glucose metabolism, NO metabolism and modulated apoptosis, in correlation with tumor size, without toxicity and influence on biochemical blood and hematological tests. The administration of metformin in two-drug combination with deoxycholic acid, caffeine, itraconazole, nitroglycerin, disulfiram or diclofenac may be recommended for further clinical investigations in oncology. [ABSTRACT FROM AUTHOR]

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The venom-containing barb attached to their 'whip-like' tail provides stingrays a defensive mechanism for evading predators such as sharks. From human encounters, dermal stingray envenomation is characterized by intense pain often followed by tissue necrosis occurring over several days to weeks. The bioactive components in stingray venoms (SRVs) and their molecular targets and mechanisms that mediate these complex responses are not well understood. Given the utility of venom-derived proteins from other venomous species for biomedical and pharmaceutical applications, we set out to characterize the bioactivity of SRV extracts from three local species that belong to the Dasyatoidea 'whiptail' superfamily. Multiple cell-based assays were used to quantify and compare the in vitro effects of these SRVs on different cell lines. All three SRVs demonstrated concentration-dependent growth-inhibitory effects on three different human cell lines tested. In contrast, a mouse fibrosarcoma cell line was markedly resistant to all three SRVs, indicating the molecular target(s) for mediating the SRV effects are not expressed on these cells. The multifunctional SRV responses were characterized by an acute disruption of cell adhesion leading to apoptosis. These findings aim to guide future investigations of individual SRV proteins and their molecular targets for potential use in biomedical applications. [ABSTRACT FROM AUTHOR]

The understanding that tumor cells might evade immunity through various mutations and the potential of an augmented immune system to eliminate abnormal cells led to the idea of utilizing platelet-rich fibrin (PRF), a blood concentrate containing the body's immune elements as an adjunctive therapy for localized tumors. This study is the first that evaluated the effect of PRF generated with different relative centrifugal forces (RCFs) on osteoblastic and fibroblastic tumor cell lines MG63 and HT1080 with regard to cell viability, cytokine and growth factor release, and the gene expression of factors related to the cell cycle and apoptosis. Our findings could demonstrate decreased cell proliferation of MG63 and HT1080 when treated indirectly with PRF compared to cell cultures without PRF. This effect was more distinct when the cells were treated with low-RCF PRF, where higher concentrations of growth factors and cytokines with reduced RCFs can be found. Similar patterns were observed when assessing the regulation of gene expression related to the cell cycle and apoptosis in both MG63 and HT1080 cells treated with PRF. Despite variations, there was a consistent trend of an up-regulation of tumor-suppressive genes and a down-regulation of anti-apoptotic genes in both cell types following treatment with high- and, particularly, low-RCF PRF formulations. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the role of Troponin T1 (TNNT1) in paclitaxel (PTX) resistance and tumor progression in breast cancer (BC). Methods: Differentially expressed genes were obtained from the GSE4298 and GSE90564 datasets. Hub genes were isolated from protein–protein interaction networks and further validated by real‐time quantitative polymerase chain reaction. The effect of TNNT1 on PTX resistance was determined using cell counting kit‐8, 5‐ethynyl‐2′‐deoxyuridine, wound healing, transwell, flow cytometry assays, and subcutaneous xenografted tumor model. Western blotting was used to detect proteins associated with PTX resistance, apoptosis, migration, invasion, and other key pathways. Hematoxylin–eosin and immunohistochemical staining were used to evaluate the role of TNNT1 in tumors. Results: After comprehensive bioinformatic analysis, we identified CCND1, IGF1, SFN, INHBA, TNNT1, and TNFSF11 as hub genes for PTX resistance in BC. TNNT1 plays a key role in BC and is upregulated in PTX‐resistant BC cells. TNNT1 silencing inhibited PTX resistance, proliferation, migration, and invasion while promoting apoptosis of PTX‐resistant BC cells. Tumor xenograft experiments revealed that TNNT1 silencing suppresses PTX resistance and tumor development in vivo. In addition, TNNT1 silencing inhibited the expression of proteins in the rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma1 (RAF1) pathway in vivo. Treatment with a RAS/RAF1 pathway activator reversed the inhibitory effect of TNNT1 silencing on proliferation, migration, and invasion while promoting apoptosis of PTX resistance BC cells. Conclusion: Silencing of TNNT1 suppresses PTX resistance and BC progression by inhibiting the RAS/RAF1 pathway, which is a promising biomarker and therapeutic target for drug resistance in BC. [ABSTRACT FROM AUTHOR]

AIM: To investigate the role and molecular mechanisms of SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) in ferroptosis. METHODS: (1) Human fibrosarcoma HT1080 cells were treated with dimethyl sulfoxide (DMSO) and different concentrations (31. 25, 62. 5 and 125 nmol/L) of Ras-selective lethal small molecule 3 (RSL3; ferroptosis inducer). Each treatment had 3 replicate wells of cells. The protein levels of SMARCA4 were detected by Western blot. (2) Two small interfering RNAs (siSMARCA4-1 and siSMARCA4-2) were constructed according to the SMARCA4 gene sequence. After SMARCA4 knockdown, each treatment had 3 replicate wells of cells, and the protein levels of SMARCA4 were determined by Western blot. Effects of DMSO, necrostatin 2 racemate (Nec-1s; necroptosis inhibitor), Z-VAD (OMe)-FMK (Z-VAD, pan-caspase inhibitor/ apoptosis inhibitor) and ferrostatin-1 (Fer-1, ferroptosis inhibitor) on cell viability were assessed using high-content analysis. The levels of ferroptosis indicators, including prostaglandin-endoperoxide synthase 2 (PTGS2) transcription, lipid peroxidation, reactive oxygen species (ROS), labile iron pool (LIP) and glutathione, were determined by RT-qPCR and flow cytometry. The mRNA expression levels of pivotal iron metabolism genes, ferroptosis-related ROS regulatory genes, and cholesterol synthesis-related genes were measured using RT-qPCR. Impact of cholesterol on the cell viability were assessed using high-content analysis. (3) Common differential gene analysis and gene ontology (GO) enrichment analysis were performed on published online data. RESULTS: (1) Treatment with RSL3 significantly reduced the protein level of SMARCA4 (P<0. 05). (2) Knockdown of SMARCA4 resulted in ferroptosis. (3) Knockdown of SMARCA4 did not induce ferroptosis by modulating the LIP and the transcription levels of ROS-related genes. (4) Knockdown of SMARCA4 affected the pathways associated with the cell membrane, lipid raft, and cholesterol synthesis. (5) Addition of cholesterol to cell culture medium rescued the ferroptosis induced by SMARCA4 knockdown (P<0. 01). CONCLUSION: Treatment with RSL3 reduces the protein level of SMARCA4 in human fibrosarcoma HT1080 cells, and inhibition of cholesterol synthesis by SMARCA4 knockdown leads to the ferroptosis of HT1080 cells. [ABSTRACT FROM AUTHOR]

Background: Canine oral fibrosarcomas are locally invasive malignant mesenchymal tumors and the third most frequently occurring neoplasia of oral cavity of dogs. The present study was conducted to record pathological features of oral fibrosarcomas in canines. Methods: During the study period (September 2020- April 2021), a total of 18 cases of canine oral neoplasia were reported and amongst these fibrosarcoma was diagnosed in five animals (27.78%). The blood samples were collected from all the dogs and the excised tumor mass was processed at Department of Veterinary Pathology, Co.V.Sc. and A.H., Jabalpur. Result: The hematological prof ile of all the f ive dogs showed no variation however; serum biochemical analysis revealed hypercalcemia. The serum MDA concentration was elevated in dogs with fibrosarcoma, indicating oxidative stress. The gross morphology of the tumors included red to pink colored irregular masses, hard in consistency and firmly attached to the underlying tissue. Cytologically, the impression smears revealed spindle shaped cells with round to elongated nuclei along with strands of collagen fibres. Upon histopathological examination proliferation of fibrous connective tissue was observed in the sub-mucosa. Higher magnif ication revealed several immature spindle shaped f ibroblasts along with scanty amounts of collagenous matrix. Masson's trichome staining also exhibited blue stained collagen deposition. Mitotic figures were numerous (8.4 mitosis/10 hpf). The tissue sections stained by modified silver colloid staining were examined at 1000 - magnification. Mean Ag-NOR count of the silver nitrate stained tissue sections was enumerated to be 9.15 dots/nucleus. Immunohistochemical examinat ion detected CD31 immunopositivity in the tissue sections as brown staining of the infiltrating blood vessels, indicating neovascularization of the tumor. [ABSTRACT FROM AUTHOR]

To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia. [ABSTRACT FROM AUTHOR]

An 8‐year‐old lurcher presented at the Pain Clinic of the Queen Mother Hospital following a 7‐month history of progressive right‐sided facial pain that was poorly responsive to multimodal oral analgesia. Initial investigations had revealed dental changes. Despite appropriate treatment, the patient's clinical signs had deteriorated, resulting in the inability to chew, behavioural changes, and his owner's being unable to administer oral medication, all resulting in progressive weight loss. Computed tomography imaging revealed marked soft tissue thickening of the upper lip, extending along the infraorbital canal and periorbital inflammation. The biopsy confirmed fibrosarcoma. The patient received a multimodal analgesia approach, with systemic analgesia and electroacupuncture performed perioperatively. Neurolysis of the infraorbital nerve was also attempted using an alcohol solution. Following recovery from anaesthesia, the patient showed improved comfort and ate before leaving the hospital. Initial improvement was seen for a number of days at home; however, following this, the owners reported deterioration. [ABSTRACT FROM AUTHOR]

ABSTRAT: Feline injection-site sarcomas in felines account for more than 40% of cutaneous and subcutaneous neoplasms in felines. The present study aimed to describe the macroscopic and histomorphological findings of feline application/injection sarcomas. Samples from 31 feline tumors with a history of feline application/inflammation sarcoma were re-evaluated regarding histological subtype, mitotic index and score, depth of tissue invasion, and presence of inflammation considering the location, intensity and predominant cell types. Of the 31 samples from felines diagnosed with sarcoma at the application/inflammation site, 87.15% were cats with no defined breed (NDB), with a mean age of 8.5 years. The predominant anatomical sites were the back and flank/abdomen, both with 29% (9/31), and the prevalent histological subtype was fibrosarcoma at 77.4% (24/31), followed by anaplastic giant cell sarcoma at 12.9% (4/31) and myxosarcoma 9.6% (3/31). The histological grade with the highest number of cases was III (51.6%), followed by Grade II (35.4%) and I (12.9%). The mean of the longest axis measurements varied between the different tumor grades without being significant, with the average being 2.5±2.79cm in Grade I tumors and 3.2±2.28cm in Grade II tumors. and 4.68±2.07cm in Grade III tumors. Necrosis was observed in 74.2% of tumors. The tissue inflammation score was mild to moderate in 58% of cases and severe in 32.2%, with lymphocytic and lymphoplasmacytic infiltrates being prevalent, with 25.8% each, followed by lymphoplasmohistiocytic with 22.6%. The infiltration depth was 38.7% in muscle tissue, followed by 32.2% in the subcutaneous tissue. Pleomorphism was accentuated in 51.6%. Desmoplasia was moderate in 45.1%. Satellite nodules were present in 29% of cases, and 19.4% had macrophages with intracytoplasmic content suggestive of adjuvants. Surgical margins were infiltrated (M1) in 48.4% and narrowed in 25.8% (M2). The anatomical locations observed were different from those recommended by the Vaccine-Associated Feline Sarcoma Task Force (VAFST); in most cases, the adjuvanted macrophage was not present. From this data, we can suggest that sarcomas in felines are not only correlated to the vaccine application, corroborating the hypothesis that any material, whether liquid or solid, and any chronic inflammatory process in the subcutaneous tissue of cats can induce the entity if they are predisposed to do so. The detailed histomorphological data evaluated in this study were key points and provided important information about tumor behavior, being a tool for clinical-oncological decision-making.

Introduction/Objective. Many drugs registered for various other indications can act selectively on tumor receptors, signaling pathways, metabolic processes, bioenergetic factors, enzymes, proteins and genes that regulate tumor proliferation, apoptosis, and neoangiogenesis without affecting these activities in healthy cells. Introduction of new drugs is a very long, complex, and expensive process of research. Detecting an anticancer effect in drugs already registered for other indications and forming their combinations may directly reduce the time and cost of such research. Methods. Anticancer efficacy of metformin and its combinations with caffeine, itraconazole and nitroglycerin was tested on fibrosarcoma experimentally induced by BHK21/C13 cells in Syrian golden hamsters (six animals per group, randomly allocated to control and experimental groups, doses equivalent to usual human doses). After animal sacrifice, tumors were excised and their size, biophysical characteristics, histology, and immunohistochemistry were assessed. Blood samples were collected for hematological and biochemical analyses and the main organs were toxicologically analyzed. Statistical significance was determined by one-way ANOVA followed by the Student–Newman–Keuls post hoc test. Results. Two-drug combinations of metformin with caffeine or itraconazole or nitroglycerin showed significant antitumor effects on hamster fibrosarcoma compared to control, regarding all tested tumor parameters (p < 0.05) without toxicity. Conclusion. Administration of metformin in combination with caffeine or itraconazole or nitroglycerin might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.

Introduction/Objective. Large diversity in molecular mechanisms of cancer regulation allows some marketed pleiotropic non-oncological non-toxic pharmaceuticals to be used in oncology, which reduces duration and cost of novel anticancer treatment research. To date, there are no published in vivo results on anticancer effects of certain combinations of non-oncological pleiotropic drugs (disulfiram, metformin, deoxycholic acid, mebendazole) that influence MAPK/PI3K/AKT/mTOR/NF-κB signaling. Methods. The anticancer effects of certain aforementioned repurposed drugs combinations, < 50 % LD50 (equivalent to the usual human dose) were assessed by fibrosarcoma growth kinetics (measured daily in vivo by calipers) and tumor proliferation (Ki-67, PCNA), neoangiogenesis (CD34, CD31), glucose metabolism (GLUT1), NO metabolism (iNOS) and apoptosis (COX4, cytochrome C) in hamsters, randomly allocated to control and experimental groups (six animals per group). The animals were sacrificed 19 days after BHK-21/C13 tumor inoculation. The tumors were excised, measured, and blood was collected. Biophysical, pathohistological, toxicological, hematological, and biochemical analyses were performed. Results. Disulfiram with metformin, disulfiram with deoxycholic acid and deoxycholic acid with metformin are the combinations that have shown significant antitumor effects on the fibrosarcoma growth kinetics and tumor immunohistochemical markers in hamsters (p < 0.05). All used drugs in efficacious combinations can inhibit MAPK/PI3K/AKT/mTOR/NF-κB signaling. The addition of NF-κB stimulator mebendazole to effective two-drug combinations rescued cancer growth, indicating that these pathways may be responsible for antitumor action. Conclusion. Combinations of non-oncological drugs: disulfiram with metformin, disulfiram with deoxycholic acid and deoxycholic acid with metformin have the potential to be used as effective non-toxic adjuvant anticancer therapy in oncology.

Manuka essential oil has long been used in traditional medicine, though the effects of the oil on cancer cells have limited studies. The goal of this project was to treat cancer cell lines with manuka essential oil at different concentrations and to ascertain the effects on the cell proliferation of normal fibroblast (CUA-4) and on fibrosarcoma (HT-1080) cells. Cell lines were grown on 24-well plates, and subconfluent cultures were treated with varying concentrations of manuka oil for 24 h. The effect of the oil on proliferation and viability was measured through direct cell counting using trypan blue dye exclusion and through the use of an MTT assay. As the concentration of oil increased, proliferation of all cell lines tested decreased with increasing dosage, concurrently with a decrease in MTT activity. To determine if the decrease in cell numbers observed from manuka oil treatment is the result of apoptosis, PARP cleavage assays were performed, confirming that the treatment caused apoptosis in both normal fibroblasts and fibrosarcoma cells. The stress-activated MAPK protein, JNK, was activated by manuka essential oil treatment, occurring synergistically with a decrease in MKP-1 expression.

Purpose: Patients are typically diagnosed with both hypertension and fibrosarcoma. Medical oncologists must prescribe suitable anti-hypertensive medications while considering anti-tumor drugs. Recently, immunotherapy has become prominent in cancer treatment. Nonetheless, it is unknown what role anti-hypertensive medications will play in immunotherapy. Methods: We examined the effects of six first-line anti-hypertensive medications on programmed cell death protein 1 antibody (PD1ab) in tumor treatment using a mouse model of subcutaneous fibrosarcoma. The drugs examined were verapamil, losartan, furosemide, spironolactone, captopril, and hydrochlorothiazide (HCTZ). The infiltration of CD8+ T cells was examined by immunohistochemistry. Additionally, several in vitro and in vivo assays were used to study the effects of HCTZ on human fibrosarcoma cancer cells to explore its mechanism. Results: Verapamil suppressed tumor growth and showed an improved effect on the tumor inhibition of PD1ab. Captopril did not affect tumor growth but brought an unexpected benefit to PD1ab treatment. In contrast, spironolactone and furosemide showed no effect on tumor growth but had an offset effect on the PD1ab therapy. Consequently, the survival time of mice was also significantly reduced. Notably, losartan and HCTZ, especially HCTZ, promoted tumor growth and weakened the effect of PD1ab treatment. Consistent results were observed in vivo and in vitro using the human fibrosarcoma cell line HT1080. We determined that the Solute Carrier Family 12 Member 3 (SLC12A3), a known target of HCTZ, may be the principal factor underlying its effect-enhancing properties through mechanism studies employing The Cancer Genome Atlas (TCGA) data and in vivo and in vitro assays. Conclusion: Verapamil and captopril potentiated the anti-tumor effect of PD1ab, whereas spironolactone and furosemide weakened the effect of PD1ab on tumor inhibition. Alarmingly, losartan and HCTZ promoted tumor growth and impaired the effect of PD1ab. Furthermore, we preliminarily found that HCTZ may promote tumor progression through SLC12A3. Based on this study, futher mechanism researches and clinical trials should be conducted in the future. [ABSTRACT FROM AUTHOR]

Background: Low-grade Fibromyxoid Sarcoma(LGFM)is a rare fibrosarcoma, which mainly occurs in young people and is mostly seen in the trunk and limbs. The tumor is usually FUS-CREB3L2 fusion caused by t(7;16)(q32-34;p11)chromosome translocation, and rarely FUS-CREB3L1 and EWSR1-CREB3L1 fusion. MUC4 diffuse strong positive can be used as a specific index of LGFM. LGFM is similar to Sclerosing Epithelioid Fibrosarcoma(SEF) and may have the same origin. Case presentation: We report a case of LGFM in the chest wall. A female who is 59 years old. In 2016, CT showed dense nodule shadow and focal thickening of the left pleura, the patient underwent surgery, Pathological report that low to moderate malignant fibrosarcoma(fibromyxoid type). The CT re-examination in 2021 showed that the tumors on the left chest wall were significantly larger than before. Pathological examination showed the disease is composed of alternating collagen like and mucinous areas. Under high-power microscope, the tumor cells are consistent in shape, spindle or short spindle, and the tumor cells are arranged in bundles. In local areas, the density of tumor cells is significantly increased, mixed with collagen fibers, and small focal SEF appear. The result of immunohistochemistry showed that SMA, Desmin, CD34, STAT6, S100, SOX10, HMB45 and Melan A were negative, EMA was weakly positive, MUC4 was diffuse and strongly positive, and Ki67 index was low (3%). Conclusion: Sequencing results showed that MET, EGFR, KMT2B and RET gene were mutated in LGFM, and KMT2B gene had cancer promoting effect, but there was no literature report in LGFM, which may be of certain significance for the diagnosis and treatment of LGFM. [ABSTRACT FROM AUTHOR]