Carcinoma of unknown primary site (CUP) is diagnosed only in 2-9% of all cancer cases. Adenocarcinomas account for approximately 60% of CUP, and some of these are putative lung adenocarcinomas. The frequency of driver oncogene positivity in the putative lung adenocarcinomas is unknown, and the efficacy of targeting therapies for the driver oncogene is also unknown. This is the first case report of C-ros oncogene 1 (ROS1)-rearranged putative lung adenocarcinoma presenting as CUP showing a good response to ROS1 inhibitor therapy. A 55-year-old woman presented with neck lymphadenopathy. Computed tomography and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed swelling of the bilateral supraclavicular, left accessory, mediastinal, and abdominal lymph nodes. The pathological analysis of the lymph node specimen biopsy indicated adenocarcinoma with cytokeratin 7 and thyroid transcription factor-1 positivity. Thus, this case was identified as ROS1- rearranged putative lung adenocarcinoma presenting as CUP. Oral crizotinib, an ROS1 inhibitor, was administered at a dose of 250 mg twice daily. Four weeks later, several swollen nodes showed marked improvement, and eight weeks later, FDG PET showed almost no uptake. In conclusion, putative lung adenocarcinoma presenting as CUP may involve ROS1 rearrangement, and ROS1 inhibitor therapy may be effective.
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http://dx.doi.org/10.18632/oncotarget.26233 | DOI Listing |
Cancers (Basel)
December 2024
Department of Radiation Oncology, University Hospital of Münster, West German Cancer Center (WTZ), Network Partner Site, 48149 Münster, Germany.
Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of aggressive B-cell lymphoma with a predominant onset in young patients. The minimization of potential (late) side effects is of cardinal interest for these patients. An anticipation of the individual risk profile is desirable to counsel the patient on the putative impact of radiotherapy (RT).
View Article and Find Full Text PDFInt J Toxicol
January 2025
Chemical and Preclinical Safety Department, Global Chemical and Preclinical Safety, Merck KGaA, Darmstadt, Germany.
The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.
View Article and Find Full Text PDFNat Commun
January 2025
Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
Glucose deprivation, a hallmark of the tumor microenvironment, compels tumor cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates the expression of mitochondrial-cytochrome c oxidase II (MT-CO2), a subunit essential for the respiratory chain complex IV, in facilitating glutaminolysis and sustaining tumor cell survival. Mechanistically, glucose deprivation activates Ras signaling to enhance MT-CO2 transcription and inhibits IGF2BP3, an RNA-binding protein, to stabilize MT-CO2 mRNA.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Department of Medicine, Service of Nephrology, Fribourg State Hospital, Fribourg, Switzerland.
Aim Of The Study: Tuberous sclerosis complex (TSC) is a genetic and multisystemic disorder that affects between 1/6'000 and 1/10'000 of newborns. Clinical criteria and/or genetic analysis establish the diagnosis. The mechanistic target of rapamycin (mTOR) inhibitors everolimus or sirolimus reduce the severity of several TSC-related clinical traits.
View Article and Find Full Text PDFDiscov Med
December 2024
Department of Respiratory Medicine, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230031 Hefei, Anhui, China.
Background: Chronic obstructive pulmonary disease (COPD) is a prevalent yet manageable respiratory condition. However, treatments presently used normally have side effects and cannot cure COPD, making it urgent to explore effective medications. The ginsenoside Rg3 (Rg3) has been shown to have anti-inflammatory and anti-tumor properties and can improve COPD.
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