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Diagnostic Pathology Jun 2024HER2-targeted therapies have recently emerged as an option in the management of metastatic colorectal cancer (mCRC) overexpressing HER2. However, data regarding HER2...
BACKGROUND
HER2-targeted therapies have recently emerged as an option in the management of metastatic colorectal cancer (mCRC) overexpressing HER2. However, data regarding HER2 status in primary CRC and its corresponding liver metastases are limited, potentially influencing clinical decisions. Therefore, the aim of this study was to compare the HER2 status in primary CRC and paired liver metastases.
METHODS
Patients with mCRC who were operated from their primary colorectal cancer and their corresponding synchronous or metachronous liver metastases, in the digestive surgery department of Besançon University Hospital, between April 1999 and October 2021, were included. Tissue microarrays were constructed from matched primary CRC and liver metastastic tissue samples. HER2 status was assessed by immunohistochemistry and in situ hybridization according to Valtorta's criteria.
RESULTS
A series of 108 paired primary CRC and liver metastases, including a series of multiple liver metastases originating from the same patients (n = 24), were assessed. Among the primary CRC, 89 (82.4%), 17 (15.8%) and 2 (1.8%) cases were scored 0, 1 + and 2 + respectively. In liver metastases, 99 (91.7%), 7 (6.5%) and 2 (1.8%) were scored 0, 1 + and 2, respectively. Overall, there was a 19% discrepancy rate in HER2 status between primary CRC and metastases, which increased to 21% in cases with multiple synchronous or metachronous liver metastases in a given patient. No significant difference was found between metachronous and synchronous metastases regarding the HER2 status (p = 0.237).
CONCLUSIONS
Our study highlights the temporal and spatial heterogeneity of HER2 status between primary CRC and corresponding liver metastases. These findings raise the question of a sequential evaluation of the HER2 status during disease progression, to provide the most suitable treatment strategy.
Topics: Humans; Colorectal Neoplasms; Receptor, ErbB-2; Female; Liver Neoplasms; Male; Middle Aged; Aged; Biomarkers, Tumor; Immunohistochemistry; Adult; Aged, 80 and over; In Situ Hybridization; Tissue Array Analysis
PubMed: 38909265
DOI: 10.1186/s13000-024-01508-y -
Journal of Medical Case Reports Jun 2024Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, representing less than 1% of all lung tumors. The two most common among them are adenoid cystic...
BACKGROUND
Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, representing less than 1% of all lung tumors. The two most common among them are adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Very few cases are reported in literature. We report a similar rare case of salivary gland type lung carcinoma that presented for the first time with unilateral opacification of left hemithorax.
CASE PRESENTATION
A 38-year-old man of North Indian origin, who was a a nonsmoker, presented with complaints of shortness of breath and cough for 1 year, which has increased in the last 2 months and was associated with significant weight loss. A frontal radiograph of the chest and computed tomography of the chest were performed, which showed a mass in the left upper lobe of the lung with its epicenter in the left main bronchus. A bronchoscopic guided biopsy was performed, and histopathology confirmed the diagnosis of lung carcinoma of salivary gland type (adenoid cystic carcinoma). There was invasion of major vessels, hence the patient was offered and started on palliative management instead of surgical treatment. In spite of palliative management of two cycles of chemotherapy and radiotherapy, the patient succumbed to the disease within 2 months from the time of diagnosis.
CONCLUSION
Lung carcinoma of the salivary gland type (especially adenoid cystic carcinoma) usually presents at a later stage. The resectability of the tumor depends on the involvement of the surrounding major vessels. Interestingly, these cancers have no association with smoking. The prognosis depends on the extent of the disease at the time of diagnosis. Hence, imaging plays a major role in deciding the further plan of management.
Topics: Humans; Male; Adult; Lung Neoplasms; Tomography, X-Ray Computed; Carcinoma, Adenoid Cystic; Liver Neoplasms; Fatal Outcome; Bone Neoplasms; Palliative Care
PubMed: 38909203
DOI: 10.1186/s13256-024-04607-y -
Cell Death & Disease Jun 2024TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary...
TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression.
Topics: Cholangiocarcinoma; T-Box Domain Proteins; Humans; Animals; Mice; Bile Duct Neoplasms; Carcinogenesis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Proliferation
PubMed: 38909034
DOI: 10.1038/s41419-024-06839-8 -
Journal For Immunotherapy of Cancer Jun 2024The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in...
BACKGROUND AND AIMS
The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy.
METHODS
De novo liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underlying mechanism of POFUT1-mediated immune evasion.
RESULTS
We identified POFUT1 as a crucial promoter of immune evasion in liver cancer. Notably, POFUT1 promoted HCC progression and inhibited T-cell infiltration in the xenograft tumor and de novo MYC/Trp53 mouse liver tumor models. Mechanistically, we demonstrated that POFUT1 stabilized programmed death ligand 1 (PD-L1) protein by preventing tripartite motif containing 21-mediated PD-L1 ubiquitination and degradation independently of its protein-O-fucosyltransferase activity. In addition, we further demonstrated that PD-L1 was required for the tumor-promoting and immune evasion effects of POFUT1 in HCC. Importantly, inhibition of POFUT1 could synergize with anti-programmed death receptor 1 therapy by remodeling TME in the xenograft tumor mouse model. Clinically, POFUT1 high expression displayed a lower response rate and worse clinical outcome to ICB therapies.
CONCLUSIONS
Our findings demonstrate that POFUT1 functions as a novel regulator of tumor immune evasion and inhibition of POFUT1 may be a potential therapeutic strategy to enhance the efficacy of immune therapy in HCC.
Topics: Fucosyltransferases; Liver Neoplasms; Humans; Mice; Animals; B7-H1 Antigen; Immunotherapy; Carcinoma, Hepatocellular; Tumor Escape; Tumor Microenvironment; Immune Evasion; Cell Line, Tumor
PubMed: 38908854
DOI: 10.1136/jitc-2024-008917 -
Medicina 2024Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) belong to the group of neoplasms called small round cell tumors. PNETs have been divided into central and...
Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) belong to the group of neoplasms called small round cell tumors. PNETs have been divided into central and peripheral. ES and peripheral PNETs arise from bones, soft tissues, or peripheral nerves. We present a case of hepatic ES/PNET in a healthy man that began four months before consultation with abdominal symptoms and weight loss. Upper gastrointestinal endoscopy and laboratory tests revealed no notable findings. The abdominal tomography revealed an enlarged liver due to a solid lesion that involved all its segments with intravenous contrast enhancement and large areas of necrosis. It compressed and displaced neighboring structures. Core needle biopsy of the liver lesion was performed: small round cell neoplasm. Immunohistochemistry revealed negativity for CD45, CKA1/A3, chromogranin, synaptophysin, and cytokeratins CK7 and CK20. Dim CD56 expression and CD99, FLI-1, and NKX2 positivity. He underwent chemotherapy treatment with carboplatin and etoposide for 6 cycles with clinical improvement and tolerance. Control images showed reduction of the mass with involvement of the right hepatic lobe, involvement of the inferior vena cava, infiltration of the right adrenal gland and upper pole of the right kidney. He was referred to hepatobiliary surgery for surgical resection of the residual lesion. The patient rejected the proposed surgical procedure. Our objective is to highlight the clinical and histological diagnostic challenge of this entity that requires ruling out other clinical entities.
Topics: Humans; Male; Liver Neoplasms; Sarcoma, Ewing; Tomography, X-Ray Computed; Immunohistochemistry; Adult; Neuroectodermal Tumors, Primitive, Peripheral
PubMed: 38907976
DOI: No ID Found -
Diagnostic Pathology Jun 2024Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of...
BACKGROUND
Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of β-catenin, with consequent hyperactivation of the Wnt/β-catenin signaling pathway, implicated in PCa progression and treatment resistance. To date, successful targeted treatment options for Wnt/β-catenin - driven PCa are lacking.
METHODS
We report a rare histologic transformation of a CTNNB1 (β-catenin) mutated metastatic castration resistant prostate cancer (mCRPC), clinically characterized by highly aggressive disease course. We histologically and molecularly characterized the liver metastatic tumor samples, as well as successfully generated patient-derived organoids (PDOs) and patient-derived xenograft (PDX) from a liver metastasis. We used the generated cell models for further molecular characterization and drug response assays.
RESULTS
Immunohistochemistry of liver metastatic biopsies and PDX tumor showed lack of expression of typical PCa (e.g., AR, PSA, PSAP, ERG) or neuroendocrine markers (synaptophysin), compatible with double-negative CRPC, but was positive for nuclear β-catenin expression, keratin 7 and 34βE12. ERG rearrangement was confirmed by fluorescent in situ hybridization (FISH). Drug response assays confirmed, in line with the clinical disease course, lack of sensitivity to common drugs used in mCRPC (e.g., enzalutamide, docetaxel). The casein kinase 1 (CK1) inhibitor IC261 and the tankyrase 1/2 inhibitor G700-LK showed modest activity. Moreover, despite harbouring a CTNNB1 mutation, PDOs were largely insensitive to SMARCA2/4- targeting PROTAC degraders and inhibitor.
CONCLUSIONS
The reported CTNNB1-mutated mCRPC case highlights the potential challenges of double-negative CRPC diagnosis and underlines the relevance of further translational research to enable successful targeted treatment of rare molecular subtypes of mCRPC.
Topics: Humans; Male; beta Catenin; Mutation; Prostatic Neoplasms, Castration-Resistant; Liver Neoplasms; Animals; Biomarkers, Tumor; Aged; Disease Progression
PubMed: 38907236
DOI: 10.1186/s13000-024-01511-3 -
Scientific Reports Jun 2024Our aim was to explore whether programmed death receptor-1 (PD-1) inhibitors would improve the prognosis of unresectable hepatocellular carcinoma (HCC) treated with...
Our aim was to explore whether programmed death receptor-1 (PD-1) inhibitors would improve the prognosis of unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus lenvatinib. In this single-center retrospective study, patients with unresectable HCC who underwent TACE and were administered lenvatinib with or without PD-1 inhibitors were enrolled and divided into the TACE + lenvatinib group and TACE + lenvatinib + PD-1 group. Overall survival (OS), progression-free survival (PFS) and tumor response were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1 and mRECIST). Treatment-related adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). In total, 35 eligible patients with unresectable HCC were included; 82.9% of patients had Hepatitis B virus (HBV) infection, and 88.6% of patients had liver cirrhosis. A total of 88.6% of patients had multiple tumors, and the median diameter of the largest tumor was 10.1 cm. A total of 14.3% of patients had extrahepatic metastasis, and 51.4% of patients had portal vein tumor thrombus. The percentages of BCLC stages A, B and C were 5.7%, 28.6% and 65.7%, respectively. There were 16 patients in the TACE + lenvatinib group and 19 patients in the TACE + lenvatinib + PD-1 group. The median follow-up time was 7.7 months (ranging from 1.7 to 31.6 months). Neither group reached the median overall survival. Under RECIST v1.1 criteria, the median PFS was 10.4 and 7.9 months in the TACE + lenvatinib and TACE + lenvatinib + PD-1 groups (HR, 1.13; 95% CI 0.45-2.84; p = 0.80), the objective response rates (ORR) were 31.3% and 31.6% (p > 0.05), and the disease control rates (DCR) were 93.8% and 78.9% (p > 0.05), respectively. Under mRECIST criteria, the median PFS was 10.4 and 10.1 months (HR, 0.98; 95% CI 0.38-2.54, p = 0.97), the ORR was 62.5% and 63.2% (p > 0.05), and the DCR was 93.8% and 73.7% (p > 0.05), respectively. Overall, AEs were relatively similar between the two groups. PD-1 inhibitors did not improve the PFS and tumor response of unresectable HCC treated with TACE plus lenvatinib. Hepatitis B infection, liver cirrhosis, portal vein tumor thrombus, multiple tumors and large tumor diameter may be potential factors that affect the efficacy of PD-1 inhibitors but need further validation.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Quinolines; Male; Female; Phenylurea Compounds; Retrospective Studies; Chemoembolization, Therapeutic; Middle Aged; Aged; Prognosis; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Adult
PubMed: 38906915
DOI: 10.1038/s41598-024-63571-1 -
Noise & HealthThe effectiveness of family music therapy for patients with advanced palliative care hepatocellular carcinoma and their main caregivers was investigated.
OBJECTIVE
The effectiveness of family music therapy for patients with advanced palliative care hepatocellular carcinoma and their main caregivers was investigated.
METHODS
The clinical data of liver cancer patients and their main caregivers admitted to Wuwei City People's Hospital from August 2022 to April 2023 were retrospectively analysed. Patients were divided into observation group A and control group A according to whether they received family music therapy, and caregivers were divided into control group B and observation group B. The general demographic data, self-rating depression scale (SDS), self-rating anxiety scale (SAS), cancer-related fatigue scale (CFS), Pittsburgh sleep quality index (PSQI), anticipatory grief scale (AGS), and caregiver burden inventory (CBI) scores of the patients and their primary caregivers were collected. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Then, data were analysed using t-test and chi-squared (χ2) test.
RESULTS
After 1:1 PSM, 45 samples were included in each group. Before management, no significant differences in SDS, SAS, AGS, CFS, PSQI and CBI scores were found among the groups (P > 0.05). After management, the SDS, SAS and CFS scores of observation group A were lower than those of control group A (P < 0.05). The AGS, PSQI and CBI scores of observation group B were lower than those of control group B (P < 0.05).
CONCLUSIONS
The effect of family music supplement therapy is ideal, which can relieve the negative emotions of patients, reduce the degree of cancer-related fatigue, enhance the sleep quality of the main caregivers and reduce anticipatory grief and the burden of care.
Topics: Humans; Music Therapy; Palliative Care; Male; Caregivers; Female; Retrospective Studies; Middle Aged; Liver Neoplasms; Aged; Adult; Carcinoma, Hepatocellular
PubMed: 38904811
DOI: 10.4103/nah.nah_17_24 -
Mikrochimica Acta Jun 2024Hepatocellular carcinoma (HCC) is the most common liver malignancy and is characterized by increasing incidence and high mortality rates. Current methods for the...
Hepatocellular carcinoma (HCC) is the most common liver malignancy and is characterized by increasing incidence and high mortality rates. Current methods for the screening and diagnosis of HCC exhibit inherent limitations, highlighting the ever-growing need for the development of new methods for the early diagnosis of HCC. The aim of this work was to develop a novel electrochemical aptasensor for the detection of HepG2 cells, a type of circulating tumor cells that can be used as biomarkers for the early detection of HCC. A carbon screen-printed electrode was functionalized with a composite suspension containing graphene oxide, chitosan, and polyaniline nanoparticles to increase the electrode surface and provide anchoring sites for the HepG2 cell-specific aptamer. The aptamer was immobilized on the surface of the functionalized electrode using multipulse amperometry, an innovative technique that significantly reduces the time required for aptamer immobilization. The innovative platform was successfully employed for the first time for the amplification-free detection of HepG2 cells in a linear range from 10 to 200,000 cells/mL, with a limit of detection of 10 cells/mL. The platform demonstrated high selectivity and stability and was successfully used for the detection of HepG2 cells in spiked human serum samples with excellent recoveries.
Topics: Humans; Hep G2 Cells; Aptamers, Nucleotide; Liver Neoplasms; Electrochemical Techniques; Carcinoma, Hepatocellular; Graphite; Biosensing Techniques; Limit of Detection; Aniline Compounds; Electrodes; Chitosan
PubMed: 38904692
DOI: 10.1007/s00604-024-06479-x -
International Journal of Biological... 2024Stable infiltration of myeloid cells, especially tumor-associated M2 macrophages, acts as one of the essential features of the tumor immune microenvironment by promoting...
Stable infiltration of myeloid cells, especially tumor-associated M2 macrophages, acts as one of the essential features of the tumor immune microenvironment by promoting the malignant progression of hepatocellular carcinoma (HCC). However, the factors affecting the infiltration of M2 macrophages are not fully understood. In this study, we found the molecular subtypes of HCC with the worst prognosis are characterized by immune disorders dominated by myeloid cell infiltration. Myeloid cell nuclear differentiation antigen (MNDA) was significantly elevated in the most aggressive subtype and exhibited a positively correlation with M2 infiltration and HCC metastasis. Moreover, MNDA functioned as an independent prognostic predictor and has a good synergistic effect with some existing prognostic clinical indicators. We further confirmed that MNDA was primarily expressed in tumor M2 macrophages and contributed to the enhancement of its polarization by upregulating the expression of the M2 polarization enhancers. Furthermore, MNDA could drive the secretion of M2 macrophage-derived pro-metastasis proteins to accelerate HCC cells metastasis both and . In summary, MNDA exerts a protumor role by promoting M2 macrophages polarization and HCC metastasis, and can serve as a potential biomarker and therapeutic target for HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Humans; Macrophages; Myeloid Cells; Animals; Cell Line, Tumor; Mice; Male; Tumor Microenvironment; Female; Neoplasm Metastasis
PubMed: 38904028
DOI: 10.7150/ijbs.91877