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Cancers May 2024The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing;...
The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies.
PubMed: 38791952
DOI: 10.3390/cancers16101874 -
Author Correction: Epidemiology, treatment and outcomes of primary renal sarcomas in adult patients.Scientific Reports May 2024
PubMed: 38789511
DOI: 10.1038/s41598-024-62573-3 -
Tislelizumab combined with GT chemotherapy for intimal sarcoma of inferior vena cava: A case report.Medicine May 2024Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack...
RATIONALE
Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack of standardized treatment and methods.
PATIENT CONCERNS
A 54-year-old female patient presented to Fenghua District People's Hospital with a post-active cough and hemoptysis and was subsequently referred to our hospital.
DIAGNOSES
The patient was pathologically diagnosed as intimal sarcoma of IVC complicating multiple intrapulmonary metastases. Chest CT revealed left lung malignant tumor with multiple intrapulmonary metastases; while enhanced upper abdominal CT showed cancer embolus of IVC with extension to right atrium and bilateral renal veins. Besides, hematoxylin and eosin staining suggested intimal sarcoma of veins. Immunohistochemical staining showed positivity for PD-L1, Ki-67, CD31, Desmin and ERG.
INTERVENTIONS
The patient initially received GT chemotherapy (gemcitabine injection + docetaxel). Then, immunotherapy (tislelizumab) was added based on the results of genetic testing (TP53 gene mutation).
OUTCOMES
The disease was stabilized after receiving the treatment.
LESSONS
Given the lack of characteristic clinical manifestations in patients with intimal sarcoma of IVC, imaging examination combined with immunohistochemical index were helpful for diagnosis of intimal sarcoma of IVC. Furthermore, the combination of tislelizumab and GT chemotherapy was feasible in such patients with positive PD-L1 expression and TP53 mutation.
Topics: Humans; Female; Middle Aged; Vena Cava, Inferior; Sarcoma; Antibodies, Monoclonal, Humanized; Vascular Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Gemcitabine; Deoxycytidine; Lung Neoplasms
PubMed: 38788046
DOI: 10.1097/MD.0000000000038056 -
Frontiers in Immunology 2024A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical...
A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical trial with CTLA4 and PD1 inhibitors. He had received pneumococcal and meningococcal vaccines post-splenectomy. On week 10, he developed grade 3 immune-related colitis, successfully treated with the anti-tumor necrosis factor-alpha inhibitor infliximab and steroids. After 4 cycles of treatment, scans showed partial response. He resumed anti-PD1 therapy, and 6 hours after the second dose of anti-PD1 he presented to the emergency room with hematemesis, hematochezia, hypotension, fever, and oxygen desaturation. Laboratory tests demonstrated acute renal failure and septicemia (). He died 12 hours after the anti-PD1 infusion from overwhelming post-splenectomy infection (OPSI). Autopsy demonstrated non-viable liver tumors among other findings. In conclusion, patients undergoing immunotherapy and with prior history of asplenia should be monitored closely for OPSI as they may be at increased risk.
Topics: Humans; Splenectomy; Male; Hemangiosarcoma; Splenic Neoplasms; Fatal Outcome; Liver Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy; Adult; Pneumococcal Infections; Programmed Cell Death 1 Receptor; CTLA-4 Antigen
PubMed: 38779675
DOI: 10.3389/fimmu.2024.1366271 -
Scientific Reports May 2024Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers...
Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55-69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000-2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70-84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics.
Topics: Humans; Kidney Neoplasms; Male; Female; United States; Aged; Middle Aged; Incidence; Kidney Pelvis; Adult; SEER Program; Aged, 80 and over; Young Adult; Adolescent; Child; Child, Preschool; Infant; COVID-19; Carcinoma, Renal Cell
PubMed: 38760399
DOI: 10.1038/s41598-024-61748-2 -
Journal of Thoracic Disease Apr 2024Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a...
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a tyrosine kinase inhibitor, is clinically used to treat pulmonary fibrosis. At present, only nintedanib is on the market for the treatment of pulmonary fibrosis. Pazopanib is a drug for the treatment of renal cell carcinoma and advanced soft tissue sarcoma.
METHODS
In this study, we explored whether pazopanib can attenuate bleomycin (BLM)-induced pulmonary fibrosis and explored its antifibrotic mechanism. and investigations were carried out to investigate the efficacy and mechanism of action of pazopanib in pulmonary fibrosis.
RESULTS
experiments showed that pazopanib can alleviate pulmonary fibrosis caused by BLM, reduce the degree of collagen deposition and improve lung function. experiments showed that pazopanib suppressed transforming growth factor-β1 (TGF-β1)-induced myofibroblast activation and promoted apoptosis and autophagy in myofibroblasts. Further mechanistic studies demonstrated that pazopanib inhibited the TGF-β1/Smad and non-Smad signaling pathways during fibroblast activation.
CONCLUSIONS
In conclusion, pazopanib attenuated BLM-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway. Pazopanib inhibits myofibroblast activation, migration, autophagy, apoptosis, and extracellular matrix (ECM) buildup by downregulating the TGF-β1/Smad signal route and the TGF-β1/non-Smad signal pathway. It has the same target as nintedanib and is a tyrosine kinase inhibitor.
PubMed: 38738240
DOI: 10.21037/jtd-23-1349 -
Gossypiboma mimicking a low-grade sarcoma and presenting twenty years after a renal transplantation.Indian Journal of Pathology &... May 2024
PubMed: 38727418
DOI: 10.4103/ijpm.ijpm_660_23 -
Advances in Radiation Oncology Jun 2024We investigated whether pulmonary metastases from historically considered radioresistant primaries would have inferior local control after radiation therapy than those...
Radioresistant Pulmonary Oligometastatic and Oligoprogressive Lesions From Nonlung Primaries: Impact of Histology and Dose-Fractionation on Local Control After Radiation Therapy.
PURPOSE
We investigated whether pulmonary metastases from historically considered radioresistant primaries would have inferior local control after radiation therapy than those from nonradioresistant nonlung primaries, and whether higher biologically effective dose assuming alpha/beta=10 (BED10) would be associated with superior local control.
METHODS AND MATERIALS
We identified patients treated with radiation therapy for oligometastatic or oligoprogressive pulmonary disease to 1 to 5 lung metastases from nonlung primaries in 2013 to 2020 at a single health care system. Radioresistant primary cancers included colorectal carcinoma, endometrial carcinoma, renal cell carcinoma, melanoma, and sarcoma. Nonradioresistant primary cancers included breast, bladder, esophageal, pancreas, and head and neck carcinomas. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare local recurrence-free survival (LRFS), new metastasis-free survival, progression-free survival, and overall survival.
RESULTS
Among 114 patients, 73 had radioresistant primary cancers. The median total dose was 50 Gy (IQR, 50-54 Gy) and the median number of fractions was 5 (IQR, 3-5). Median follow-up time was 59.6 months. One of 41 (2.4%) patients with a nonradioresistant metastasis experienced local failure compared with 18 of 73 (24.7%) patients with radioresistant metastasis (log-rank = .004). Among radioresistant metastases, 12 of 41 (29.2%) patients with colorectal carcinoma experienced local failure compared with 6 of 32 (18.8%) with other primaries (log-rank = .018). BED10 ≥100 Gy was associated with decreased risk of local recurrence. On univariable analysis, BED10 ≥100 Gy (hazard ratio [HR], 0.263; 95% CI, 0.105-0.656; = .004) was associated with higher LRFS, and colorectal primary (HR, 3.060; 95% CI, 1.204-7.777; = .019) was associated with lower LRFS, though these were not statistically significant on multivariable analysis. Among colorectal primary patients, BED10 ≥100 Gy was associated with higher LRFS (HR, 0.266; 95% CI, 0.072-0.985; = .047) on multivariable analysis.
CONCLUSIONS
Local control after radiation therapy was encouraging for pulmonary metastases from most nonlung primaries, even for many of those classically considered to be radioresistant. Those from colorectal primaries may benefit from testing additional strategies, such as resection or systemic treatment concurrent with radiation.
PubMed: 38699671
DOI: 10.1016/j.adro.2024.101500 -
Scientific Reports May 2024To assess epidemiology, clinical presentation, treatment and overall survival of adult patients with renal sarcomas, the 2004-2016 SEER and NCDB databases were queried...
To assess epidemiology, clinical presentation, treatment and overall survival of adult patients with renal sarcomas, the 2004-2016 SEER and NCDB databases were queried for adult patients diagnosed with renal sarcoma, calculating average annual age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) as well as overall survival (OS). In n = 1279 included renal sarcoma patients, AAIR remained constant over the study period (average 0.53 cases/1million; AAPC = 0.7, p = 0.6). Leiomyosarcoma (AAIR 0.14 cases/1 million) and malignant rhabdoid tumors (0.06 cases/1 million) were most common. Sarcoma histiotypes demonstrated considerable heterogeneity regarding demographic and cancer-related variables. Patients presented with advanced local extent (T3 33.3%; T4 14.2%) or distant metastases (29.1%) and commonly underwent surgical resection (81.6%). Longer OS was independently associated with younger age, female sex, lower comorbidity index, low T stage, negative surgical margins, absence of tumor necrosis or distant metastases and leiomyosarcoma histiotype (multivariable p < 0.05 each). Treatment efficacy varied according to sarcoma histiotype (interaction p < 0.001). Accounting for 0.25% of renal malignancies, renal sarcomas include 43 histiotypes with distinct epidemiology, clinical presentation, outcomes and sensitivity to systemic therapy, thereby reflecting soft-tissue sarcoma behavior. Renal sarcoma treatment patterns follow recommendations by renal cancer guidelines with surgical resection as the cornerstone of therapy.
Topics: Humans; Male; Female; Middle Aged; Sarcoma; Kidney Neoplasms; Aged; Adult; Treatment Outcome; Incidence; SEER Program; Aged, 80 and over
PubMed: 38693188
DOI: 10.1038/s41598-024-60174-8 -
Cureus Apr 2024Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods ...
Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods Between January 2015 and March 2023, we retrospectively evaluated 1087 patients of both sexes who underwent cranial magnetic resonance imaging (MRI) for a preliminary diagnosis of intracranial malignancy in the radiology department of our hospital. Two radiologists with six and 10 years of experience in MRI examination assessed the relationship between primary and metastatic tumors and the fornix. Results Involvement of the fornix was diagnosed in 29 of the 1087 patients (2.66%), of which fornix was affected by metastatic lesions in 14 patients (48.2%) and primary tumors in 15 patients (51.7%). The majority of metastatic lesions were from lung and breast cancers, with other tumor types including osteosarcoma, renal cell carcinoma, pancreatic adenocarcinoma, pleomorphic sarcoma, and diffuse large B-cell lymphoma. Among all primary tumors, glioblastoma was the most common primary brain tumor invading the fornix, with other diagnoses including diffuse astrocytoma, medulloblastoma, and anaplastic oligodendroglioma. Metastatic and primary brain tumors affecting the fornix were detected over a broad timeline, from the time of diagnosis up to 120 months after diagnosis. A retrospective evaluation of medical records revealed memory deficits in four patients. Conclusion The fornix can be affected by both metastatic and primary brain tumors. It is crucial to understand the relevant neuroanatomical relationships when evaluating lesions that affect the fornix.
PubMed: 38689678
DOI: 10.7759/cureus.57612