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1.
Skeletal Radiol ; 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39379548

RESUMEN

Synovial chondrosarcoma (CHS) is a rare malignant tumor arising from the synovial tissue and is often associated with synovial chondromatosis. Herein, we present a unique case of primary synovial CHS in the shoulder joint without evidence of synovial chondromatosis. A 60-year-old man presented to our hospital with a complain of left shoulder pain that persisted for 6 years, which was initially misdiagnosed as synovitis. Radiography revealed an osteolytic lesion involving the humerus and the scapula. Histologically, the tumor exhibited features of grade 2 synovial CHS, infiltrating the trabecular bones and intra-articular space. Wide resection led to a 9-year recurrence-free survival. This case underscores the challenges in diagnosing and managing synovial CHS, particularly in cases with atypical presentations lacking synovial chondromatosis, necessitating careful follow-up and adequate surgical intervention.

2.
Sci Rep ; 14(1): 22973, 2024 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-39362949

RESUMEN

PRAME (PReferentially expressed Antigen in MElanoma) was first identified as a malignant melanoma-specific antigen. Recently, a few cases of fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) were shown to have positivity for PRAME, while conventional dermatofibrosarcoma protuberans (C-DFSP) was negative. Because PRAME may be of diagnostic utility in FS-DFSP and is raising expectations as a new immunotherapy target, we examined the positivity of PRAME in FS-DFSP. Twenty-one cases of FS-DFSP and age/sex/location-matched cases of C-DFSP as a control group were examined by immunohistochemistry for CD34 and PRAME. The results were then evaluated by H-score, which was objectively and semi-quantitatively calculated using the open-source bioimaging analysis software QuPath. The results revealed that the PRAME H-score in FS-DFSP was significantly higher than that in C-DFSP (p = 0.0137). As for CD34, the H-score in FS-DFSP was significantly lower than that in C-DFSP (p < 0.001). Using these two immunohistochemical analyses in combination, the sensitivity and specificity for the diagnosis of FS-DFSP were 86% and 90%, respectively. Double staining of CD34 and PRAME revealed that PRAME-positive and CD34-positive areas did not overlap. This is the largest study to examine PRAME expression in FS-DFSP, and it confirmed the usefulness of PRAME in diagnosing this condition.


Asunto(s)
Antígenos CD34 , Antígenos de Neoplasias , Dermatofibrosarcoma , Humanos , Dermatofibrosarcoma/patología , Dermatofibrosarcoma/metabolismo , Dermatofibrosarcoma/diagnóstico , Dermatofibrosarcoma/genética , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/genética , Femenino , Masculino , Adulto , Persona de Mediana Edad , Antígenos CD34/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/genética , Biomarcadores de Tumor/metabolismo , Inmunohistoquímica , Anciano , Fibrosarcoma/metabolismo , Fibrosarcoma/patología , Fibrosarcoma/genética , Adulto Joven
3.
Int J Clin Oncol ; 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39441454

RESUMEN

BACKGROUND: Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated. MATERIALS AND METHODS: We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. RESULTS: Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan-Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group. CONCLUSION: Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.

4.
Nat Commun ; 15(1): 9033, 2024 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-39426955

RESUMEN

Despite the success of immune checkpoint blockade (ICB) therapy for esophageal squamous cell cancer, the key immune cell populations that affect ICB efficacy remain unclear. Here, imaging mass cytometry of tumor tissues from ICB-treated patients identifies a distinct cell population of CD39+PD-1+CD8+ T cells, specifically the TCF1+ subset, precursor exhausted T (CD39+ Tpex) cells, which positively correlate with ICB benefit. CD39+ Tpex cells are predominantly in the stroma, while differentiated CD39+ exhausted T cells are abundantly and proximally within the parenchyma. Notably, CD39+ Tpex cells are concentrated within and around tertiary lymphoid structure (TLS). Accordingly, tumors harboring TLSs have more of these cells in tumor areas than tumors lacking TLSs, suggesting Tpex cell recruitment from TLSs to tumors. In addition, circulating CD39+ Tpex cells are also increased in responders following ICB therapy. Our findings show that this unique subpopulation of CD39+PD-1+CD8+ T cells is crucial for ICB benefit, and suggest a key role in TLS-mediated immune responses against tumors.


Asunto(s)
Apirasa , Linfocitos T CD8-positivos , Neoplasias Esofágicas , Inhibidores de Puntos de Control Inmunológico , Receptor de Muerte Celular Programada 1 , Estructuras Linfoides Terciarias , Humanos , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Apirasa/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Antígenos CD/metabolismo , Antígenos CD/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Femenino , Masculino , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos
5.
Int Cancer Conf J ; 13(4): 481-487, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39398906

RESUMEN

Mucoepidermoid carcinoma is the most prevalent malignancy in the salivary gland and is sporadic in the breast. Here, we report a case of breast mucoepidermoid carcinoma with a rare CREB-regulated transcription coactivator 3-mastermind-like transcriptional coactivator 2 (CRTC3-MAML2) fusion. A 23-year-old female was admitted to our hospital with a left breast palpable mass. Histologic findings of the core-needle biopsy indicated breast cancer. The section revealed a squamoid tumor-cell proliferation with enlarged nuclei and eosinophilic cytoplasm among smaller intermediate cells and abundant cystic spaces containing secretory materials. The features were compatible with mucoepidermoid carcinoma in low-grade, confirmed by detecting the CRTC3-MAML2 fusion using reverse transcription polymerase chain reaction and direct sequencing. We only administered tamoxifen postoperatively without other adjuvant therapy because her tumor partially expressed hormonal receptors. No signs indicate a recurrence or metastasis in our over 3 year follow-up. The genetic analysis helps in definitively diagnosing breast mucoepidermoid carcinoma, and the treatment strategy should be considered based on the histologic findings.

6.
Pathol Res Pract ; 263: 155642, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39368366

RESUMEN

Identifying the primary site of metastatic squamous cell carcinoma in lymph nodes can be challenging. An immunohistochemistry (IHC) analysis recently revealed that high-risk human papillomavirus (HR-HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) typically show overexpression of p16 protein and a partial loss pattern of Rb. Nevertheless, the status of these markers in metastatic lesions is still unclear. In this study, we examined p16 and Rb expression status by IHC and transcriptionally active HR-HPV infection by mRNA in situ hybridization in paired primary and metastatic SCC lesions. A total of 50 patients with OPSCCs (n=17), hypopharyngeal SCCs (n=16), laryngeal SCCs (n=6), or uterine cervical SCCs (n=11) were enrolled. HR-HPV and p16 were positive in 21/50 (42 %) and 23/50 (46 %) patients, respectively. Primary and metastatic lesions showed concordant results for those three markers in individual patients. Among the p16-positive patients (n=23), HPV-positive cases typically showed a partial loss of Rb (n=20) and, rarely, a complete loss of Rb (n=1), whereas HPV-negative cases showed preserved Rb expression (n=2). All 27 p16-negative cases lacked HPV infection, while preserved expression and complete loss of Rb were observed in 26 and 1 of the p16-negative cases, respectively. Compared to standalone p16, the combination of p16 overexpression and Rb-partial/complete loss showed equally excellent sensitivity and negative predictive value (each 100 %) as well as improved specificity (100 % versus 93.1 %) and positive predictive value (100 % versus 91.3 %). Our results suggest that combining p16 and Rb expression patterns may be helpful in screening for HR-HPV infection in metastatic lymph nodes and in estimating the primary site of SCC.

7.
Exp Dermatol ; 33(10): e15196, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39422290

RESUMEN

Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer, but treatments for advanced cases have limited efficacy. Trophoblast cell-surface antigen 2 (TROP2) is a cell-surface protein that is widely expressed in various tumours, where it exerts significant influence over critical processes such as tumour cell growth, apoptosis, migration, invasion and metastasis. Sacituzumab govitecan, an antibody-drug conjugate (ADC) targeting TROP2, is emerging as a promising strategy for anticancer therapy. In this study, we investigated TROP2 expression in cSCC tissues from 51 patients and evaluated its function in the A431 human SCC cell line. Immunohistochemical analysis revealed TROP2 expression on the plasma membrane of cSCC tissues and A431 cells. A431 cells showed sensitivity to sacituzumab govitecan with a significant concentration-dependent decrease in viable cell number. In addition, Knockdown of TROP2 resulted in decreased expression of cyclin D1 and BCL-2, along with reduced cell viability. Knockdown of TROP2 also resulted in decreased expression of vimentin, along with reduced migratory capacity. These findings suggest that TROP2 plays a crucial role in cSCC cell proliferation and migration, and highlight the potential of sacituzumab govitecan as a promising therapeutic option for cSCC.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Antígenos de Neoplasias , Carcinoma de Células Escamosas , Moléculas de Adhesión Celular , Movimiento Celular , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Supervivencia Celular/efectos de los fármacos , Inmunohistoquímica , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Femenino , Técnicas de Silenciamiento del Gen , Ciclina D1/metabolismo , Vimentina/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Anciano , Proliferación Celular/efectos de los fármacos , Persona de Mediana Edad , Masculino , Apoptosis/efectos de los fármacos , Camptotecina/análogos & derivados
8.
Surg Case Rep ; 10(1): 231, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39377932

RESUMEN

BACKGROUND: Management of patients with colorectal liver metastases (CRLMs) requires a multidisciplinary approach. For patients with progression of RAS mutant tumors, the choice of angiogenesis inhibitors can be controversial. Here, we report a patient with RAS mutant CRLMs achieving long-term disease-free survival with repeated R0 resections and perioperative treatment, especially aflibercept + FOLFIRI (5-fluorouracil, levofolinate, irinotecan), which may have prevented long-term recurrence. CASE PRESENTATION: The patient was a 37 year-old woman diagnosed with RAS mutant transverse colon cancer with 19 LMs. As the metastases were limited to the liver, we introduced systemic chemotherapy aiming at conversion surgery. After six cycles of bevacizumab + FOLFOXIRI (5-fluorouracil, levofolinate, oxaliplatin, irinotecan), we performed partial hepatectomy for all LMs, and left hemicolectomy for the primary tumor after another four cycles of bevacizumab + FOLFIRI. Three months after surgery, the patient presented with massive ovarian metastases with carcinomatous ascites. We conducted bilateral oophorectomy, and initiated aflibercept + FOLFIRI therapy considering the possibility of resistance to bevacizumab. The patient was recurrence-free for 2 years during aflibercept + FOLFIRI treatment. After its discontinuation, two distant metastases developed. Both were resectable and the patient achieved recurrence-free survival of 2 years and 3 months after the last operation (6 years since initiation of treatment), without additional chemotherapy. CONCLUSIONS: We believe that multidisciplinary treatment aimed at complete resection could lead to long-term survival even in patients with repeated recurrence of CRLMs. Aflibercept + FOLFIRI could be effective in controlling metastasis of RAS mutant colon cancer even after treatment with bevacizumab.

9.
Intern Med ; 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39428537

RESUMEN

A 75-year-old man diagnosed with esophageal cancer and lung metastasis received a combination of fluorouracil, cisplatin, and pembrolizumab. During pembrolizumab maintenance therapy, lymphoproliferative lesions at the lips and mouth and multiple lymph node swellings appeared. Histologically, Epstein-Barr virus (EBV)-encoded RNA was positive, and EBV-DNA was detected in the blood. The patient was diagnosed with other iatrogenic immunodeficiency-associated lymph proliferative disorders (OIIA-LPDs) related to EBV activation induced by pembrolizumab. Rituximab was administered, resulting in the improvement of the OIIA-LPD. The emergence of an OIIA-LPD merits close attention in patients receiving immune checkpoint inhibitors.

10.
Clin Cancer Res ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264265

RESUMEN

PURPOSE: We aim to clarify the precise function of Transformed growth factor-beta 1 activated kinase-1 (TAK1) in cancer-associated fibroblasts (CAFs) within human pancreatic ductal adenocarcinoma (PDAC) by investigating its role in cytokine-mediated signaling pathways. EXPERIMENTAL DESIGN: The expression of TAK1 in pancreatic cancer was confirmed by TCGA data and human pancreatic cancer specimens. CAFs from freshly resected PDAC specimens were cultured and used in a three-dimensional model for direct and indirect co-culture with PDAC tumors to investigate TAK1 function. Additionally, organoids from KPC (LSL-K-RasLSLG12D/+; LSL-p53R172H/+; Pdx1-Cre) mice were mixed with CAFs and injected subcutaneously into C57BL/6 mice to explore in vivo functional interactions of TAK1. RESULTS: TCGA data revealed significant upregulation of TAK1 in PDAC, associating with a positive correlation with the T-cell exhaustion signature. Knockdown of TAK1 in CAFs decreased the iCAF signature and increased the myCAF signature both in vitro and in vivo. The absence of TAK1 hindered CAF proliferation, blocked several inflammatory factors via multiple pathways associated with immunosuppression, and hindered EMT, outgrowth in vitro in spheroid co-cultures with PDAC cells. Additionally, TAK1 inhibitor restrained tumor growth, increased CD4+ and CD8+ T cell abundance, and reduced immunosuppressive cells present in vivo. CONCLUSIONS: Blocking the TAK1+CAF phenotype leads to the conversion of protumorigenic CAFs to antitumorigenic CAFs. This highlights TAK1 as a potential therapeutic target, particularly in CAFs, and represents a novel avenue for combined immunotherapy in PDAC.

11.
Anticancer Res ; 44(10): 4593-4603, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39348971

RESUMEN

BACKGROUND/AIM: The benefit of neoadjuvant chemotherapy (NAC) in the treatment of head and neck squamous cell carcinoma (HNSCC) remains unclear. PATIENTS AND METHODS: We retrospectively collected 30 patients with HNSCC who had undergone radical resection after NAC. We pathologically evaluated the therapeutic response to NAC, and classified the residual tumor patterns. In addition, we compared the maximum horizontal diameter on pathology with imaging. RESULTS: The residual patterns were categorized as follows: 10 cases of shrunken type, 11 cases of mixed type, and seven cases of fragmented type. The majority of underestimation cases - those cases in which the maximum horizontal diameter measured on post-NAC imaging was less than the pathological size after resection - were multifocal residual lesions, with a tendency for more frequent "positive" or "close" surgical margins. CONCLUSION: The strategy of performing NAC to reduce resection volume is not appropriate, and resection margins should be based on the assessment before NAC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Terapia Neoadyuvante , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Anciano , Estudios Retrospectivos , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/cirugía , Adulto , Quimioterapia Adyuvante , Neoplasia Residual/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
12.
Cancer Res ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288081

RESUMEN

The effect of immune checkpoint inhibitors is extremely limited in patients with pancreatic ductal adenocarcinoma (PDAC) due to the suppressive tumor immune microenvironment (TIME). Autophagy, which has been shown to play a role in anti-tumor immunity, has been proposed as a therapeutic target for PDAC. Here, single-cell RNA-sequencing of autophagy-deficient murine PDAC tumors revealed that autophagy inhibition in cancer cells induced dendritic cell (DC) activation. Analysis of human PDAC tumors substantiated a negative correlation between autophagy and DC activation signatures. Mechanistically, autophagy inhibition increased intracellular accumulation of tumor antigens, which could activate DCs. Administration of chloroquine (CQ), an autophagy inhibitor, in combination with Flt3 ligand (Flt3L)-induced DC infiltration inhibited tumor growth and increased tumor-infiltrating T lymphocytes. However, autophagy inhibition in cancer cells also induced CD8+ T cell exhaustion with high expression of immune checkpoint LAG3. A triple therapy comprising CQ, Flt3L, and an anti-LAG3 antibody markedly reduced tumor growth in orthotopic syngeneic PDAC mouse models. Thus, targeting autophagy in cancer cells and activating DCs sensitizes PDAC tumors to immune checkpoint inhibitor therapy, warranting further development of this treatment approach to overcome immunosuppression in pancreatic cancer.

13.
Surg Case Rep ; 10(1): 208, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39237696

RESUMEN

BACKGROUND: Preoperative vascular embolization is an effective strategy for managing meningiomas, neck paragangliomas, renal cell carcinomas, and bone metastasis by reducing the intraoperative bleeding volume and operation time. Although hypervascular tumors also occur in the pancreas, preoperative embolization for these tumors is not commonly practiced. We herein present a case of a giant serous cystic neoplasm (SCN) of the pancreas with significant arterial vascularity that was managed with preoperative interventional radiology and subsequently resected via pancreaticoduodenectomy. CASE PRESENTATION: A 60-year-old man presented with an 8-cm hypervascular tumor located at the head of the pancreas, identified as an SCN on pathologic examination. The tumor had increased by 13 mm over 5 years, necessitating surgical intervention. Computed tomography revealed a substantial blood supply to the tumor from the dorsal pancreatic artery and gastroduodenal artery, both branches of the superior mesenteric artery. To mitigate the risk of severe intraoperative bleeding from this giant hypervascular tumor, branches of the dorsal pancreatic artery and gastroduodenal artery were embolized using metallic coils and further secured using a gelatin sponge 1 day prior to pancreatectomy. During the laparotomy, the tumor appeared to have decreased in size, likely because of reduced distension and congestion. Despite significant adhesions to surrounding tissues secondary to prolonged compression and inflammation, the pancreaticoduodenectomy was completed successfully in 5 h and 15 min with blood loss of 763 mL. The patient was discharged on postoperative day 15 without complications. CONCLUSIONS: Preoperative arterial embolization for hypervascular pancreatic tumors might control the risk of massive intraoperative bleeding, contributing to a favorable postoperative outcome. Utilizing interventional radiology for preoperative inflow control is one of the beneficial strategies for pancreatectomy in patients with a giant SCN.

14.
J Exp Clin Cancer Res ; 43(1): 271, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39343933

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma tumors exhibit resistance to chemotherapy, targeted therapies, and even immunotherapy. Dendritic cells use glucose to support their effector functions and play a key role in anti-tumor immunity by promoting cytotoxic CD8+ T cell activity. However, the effects of glucose and lactate levels on dendritic cells in pancreatic ductal adenocarcinoma are unclear. In this study, we aimed to clarify how glucose and lactate can impact the dendritic cell antigen-presenting function and elucidate the relevant mechanisms. METHODS: Glycolytic activity and immune cell infiltration in pancreatic ductal adenocarcinoma were evaluated using patient-derived organoids and resected specimens. Cell lines with increased or decreased glycolysis were established from KPC mice. Flow cytometry and single-cell RNA sequencing were used to evaluate the impacts on the tumor microenvironment. The effects of glucose and lactate on the bone marrow-derived dendritic cell antigen-presenting function were detected by flow cytometry. RESULTS: The pancreatic ductal adenocarcinoma tumor microenvironment exhibited low glucose and high lactate concentrations from varying levels of glycolytic activity in cancer cells. In mouse transplantation models, tumors with increased glycolysis showed enhanced myeloid-derived suppressor cell infiltration and reduced dendritic cell and CD8+ T cell infiltration, whereas tumors with decreased glycolysis displayed the opposite trends. In three-dimensional co-culture, increased glycolysis in cancer cells suppressed the antigen-presenting function of bone marrow-derived dendritic cells. In addition, low-glucose and high-lactate media inhibited the antigen-presenting and mitochondrial functions of bone marrow-derived dendritic cells. CONCLUSIONS: Our study demonstrates the impact of dynamic glycolytic reprogramming on the composition of immune cells in the tumor microenvironment of pancreatic ductal adenocarcinoma, especially on the antigen-presenting function of dendritic cells.


Asunto(s)
Carcinoma Ductal Pancreático , Células Dendríticas , Glucólisis , Neoplasias Pancreáticas , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/metabolismo , Animales , Ratones , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Microambiente Tumoral , Reprogramación Celular , Línea Celular Tumoral
15.
Surg Case Rep ; 10(1): 225, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39325359

RESUMEN

BACKGROUND: Intramuscular hemangioma is an uncommon benign tumor found mainly in the limbs of adolescents and young adults. The local recurrence rate is high, ranging from 30 to 50%, necessitating wide local excision of intercostal intramuscular hemangiomas. However, preoperative diagnosis of intramuscular hemangiomas is challenging. Herein, we report a rare case of an intramuscular hemangioma arising from the chest wall. CASE PRESENTATION: A healthy 29-year-old asymptomatic man was referred to our hospital after an abnormal shadow was observed on his chest radiography. Computed tomography and magnetic resonance imaging revealed a 30-mm-sized mass in the right second intercostal space. Neoplastic lesions, such as schwannomas or solitary fibrous tumors, were included in the preoperative differential diagnosis. Tumor resection was performed using video-assisted thoracoscopic surgery. The tumor, which had a smooth surface covered with parietal pleura, was dissected from the external intercostal muscle and costal bone. Postoperative histopathological examination revealed proliferation of spindle-shaped endothelial cells arranged in a capillary vascular structure accompanied by entrapped smooth muscle fibers, adipose tissue, and muscle vessels. The final diagnosis was an intramuscular hemangioma with negative surgical margins. There was no evidence of recurrence during the 1-year postoperative follow-up period. CONCLUSION: Intramuscular hemangiomas should be considered in the differential diagnosis of chest wall tumors, particularly in young people, owing to their potential for recurrence. Moreover, postoperative follow-up may be necessary for resected intramuscular intercostal hemangiomas.

16.
J Exp Clin Cancer Res ; 43(1): 258, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261943

RESUMEN

BACKGROUND: Tumor-associated neutrophils (TANs) constitute an abundant component among tumor-infiltrating immune cells and have recently emerged as a critical player in pancreatic ductal adenocarcinoma (PDAC) progression. This study aimed to elucidate the pro-tumor mechanisms of TAN and identify a novel target for effective immunotherapy against PDAC. METHODS: Microarray and cytokine array analyses were performed to identify the mechanisms underlying the function of TANs. Human and mouse TANs were obtained from differentiated HL-60 cells and orthotopically transplanted PDAC tumors, respectively. The interactions of TANs with cancer and cytotoxic T-cells were evaluated through in vitro co-culture and in vivo orthotopic or subcutaneous models. Single-cell transcriptomes from patients with PDAC were analyzed to validate the cellular findings. RESULTS: Increased neutrophil infiltration in the tumor microenvironment was associated with poor survival in patients with PDAC. TANs secreted abundant amounts of chemokine ligand 5 (CCL5), subsequently enhancing cancer cell migration and invasion. TANs subpopulations negatively correlated with cytotoxic CD8+ T-cell infiltration in PDAC and promoted T-cell dysfunction. TANs upregulated the membranous expression of Nectin2, which contributed to CD8+ T-cell exhaustion. Blocking Nectin2 improved CD8+ T-cell function and suppressed tumor progression in the mouse model. Single-cell analysis of human PDAC revealed two immunosuppressive TANs phenotypes: Nectin2+ TANs and OLR1+ TANs. Endoplasmic reticulum stress regulated the protumor activities in TANs. CONCLUSIONS: TANs enhance PDAC progression by secreting CCL5 and upregulating Nectin2. Targeting the immune checkpoint Nectin2 could represent a novel strategy to enhance immunotherapy efficacy in PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Nectinas , Neutrófilos , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Microambiente Tumoral/inmunología , Animales , Ratones , Nectinas/metabolismo , Nectinas/genética , Neutrófilos/inmunología , Neutrófilos/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Regulación hacia Arriba , Femenino , Línea Celular Tumoral , Masculino , Modelos Animales de Enfermedad
17.
Int J Clin Oncol ; 29(11): 1746-1755, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39177879

RESUMEN

BACKGROUND: Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4 g/m2. However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6 g/m2 and 17.6 g/m2, respectively, without decreasing the FFS rates. METHODS: Subgroup-A patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 1.2 g/m2/cycle cyclophosphamide. Subgroup-B patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 2.2 g/m2/cycle cyclophosphamide, followed by six cycles (24 weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy. RESULTS: In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths. CONCLUSIONS: Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Dactinomicina , Rabdomiosarcoma Embrionario , Vincristina , Humanos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Femenino , Masculino , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Rabdomiosarcoma Embrionario/tratamiento farmacológico , Rabdomiosarcoma Embrionario/patología , Dactinomicina/uso terapéutico , Dactinomicina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adolescente , Preescolar , Niño , Japón , Adulto , Adulto Joven , Supervivencia sin Enfermedad
18.
Ann Surg Oncol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179864

RESUMEN

BACKGROUND: Ferroptosis is a cell death caused by iron-dependent accumulation of lipid peroxidation. Transferrin receptor (TFR) is a ferroptosis-related protein responsible for iron transport. The detailed biologic role of TFR in intrahepatic cholangiocarcinoma (ICC) is not fully elucidated. METHODS: The study enrolled 92 ICC patients who had undergone hepatic resection. Immunohistochemistry (IHC) assays were performed for TFR protein expression. The regulation of malignant activity and the effect on sensitivity to the ferroptosis-inducer artesunate by TFR were investigated in vitro. RESULTS: Using IHC staining, 23 patients were categorized as TFR-positive. The TFR-positive group had a significantly larger tumor size and more microscopic vascular invasion. In the multivariate analysis, TFR positivity was an independent poor prognostic factor. In vitro TFR-knockdown (KD) significantly decreased the intracellular iron levels and the cell proliferation, migration, and invasion rates. Artesunate treatment significantly decreased cell viability, whereas cisplatin promoted ferroptosis. When iron transport into cells was inhibited by TFR-KD, ferroptosis was significantly suppressed. Expression of PD-L1 was induced by cisplatin, with a further increase observed when artesunate and cisplatin were used in combination. CONCLUSIONS: Transferrin receptor is a poor prognostic factor for ICC and contributes to sensitivity to ferroptosis.

19.
J Orthop Sci ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39003183

RESUMEN

BACKGROUND: In Japan, there are currently no general guidelines for the treatment of primary malignant bone tumors. Therefore, the Japanese Orthopaedic Association established a committee to develop guidelines for the appropriate diagnosis and treatment of primary malignant bone tumors for medical professionals in clinical practice. METHODS: The guidelines were developed in accordance with "Minds Clinical Practice Guideline Development Handbook 2014″ and "Minds Clinical Practice Guideline Development Manual 2017". The Japanese Orthopaedic Association's Bone and Soft Tissue Tumor Committee established guideline development and systematic review committees, drawing members from orthopedic specialists leading the diagnosis and treatment of bone and soft tissue tumors. Pediatricians, radiologists, and diagnostic pathologists were added to both committees because of the importance of multidisciplinary treatment. Based on the diagnosis and treatment algorithm for primary malignant bone tumors, important decision-making points were selected, and clinical questions (CQ) were determined. The strength of recommendation was rated on two levels and the strength of evidence was rated on four levels. The recommendations published were selected based on agreement by 70% or more of the voters. RESULTS: The guideline development committee examined the important clinical issues in the clinical algorithm and selected 22 CQs. The systematic review committee reviewed the evidence concerning each CQ and a clinical value judgment was added by experts. Eventually, 25 questions were published and the text of each recommendation was determined. CONCLUSION: Since primary malignant bone tumors are rare, there is a dearth of strong evidence based on randomized controlled trials, and recommendations cannot be applied to all the patients. In clinical practice, appropriate treatment of patients with primary malignant bone tumors should be based on the histopathological diagnosis and degree of progression of each case, using these guidelines as a reference.

20.
Int Cancer Conf J ; 13(3): 301-305, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38962045

RESUMEN

Dedifferentiated liposarcoma is a rare cancer with a poor prognosis. A 52-year-old man presented with a chief complaint of a mass in his left scrotum. He came with suspected testicular tumor, but all the measured tumor markers were negative. Imaging test showed approximately 2 cm diameter mass accompanied by calcification with some substantial components between the testis and epididymis. Left high testicular resection was performed. The tumor had no continuity between the testis and epididymis, and the spermatic cord transection was negative. Pathological findings showed well differentiated fatty component and a dedifferentiated component around the trabecular bone-like tissue. We observed dedifferentiated dysmorphic cells mixed with fatty droplets of unequal size. Immunostaining led to the diagnosis of dedifferentiated liposarcoma. No additional postoperative therapy was performed. The possibility of dedifferentiated liposarcoma should be kept in mind even if mass is confined to the scrotum and consisted of calcification. In the case of an intrascrotal calcified mass with malignant perspective, radical surgery is highly recommended.

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