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Lung cancer is the leading cause of cancer-related mortality and approximately 5% of non–small-cell lung cancer (NSCLC) patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4. ALK inhibitors are the mainstay treatment for patients with NSCLC harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Several ALK-1 inhibitors are used in clinical practice, including crizotinib, ceritinib and alectinib. According to the package insert and published literature, treatment with several ALK-1 inhibitors appears to be associated with the development of peripheral edema and rare electrolyte disorders, kidney failure, proteinuria and an increased risk for the development and progression of renal cysts. This review introduces the different types of ALK inhibitors, focusing on their detailed kidney-related side effects in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Inflammatory myofibroblastic tumor is an infrequent lesion that is seen in the lungs, abdomen, skin, soft tissue, genital system, and mediastinum. It is rare in the oral cavity. Case presentation: A 58-year-old woman presented with a mass in the left buccal mucosa. An extensive surgical intervention was performed. On gross examination, the mass was 9.5 x 8 x 3.5 cm in size. Microscopically, the tumor included spindle-shaped myofibroblast-like cells intermingling chronic inflammatory cells. Differential diagnosis of inflammatory myofibroblastic tumor is extensive and includes benign and malignant spindle cell tumors, such as cranial fasciitis, solitary fibrous tumor, fibrosarcoma, and rhabdomyosarcoma. Conclusion: Inflammatory myofibroblastic tumors are classified as tumors of intermediate biological potential due to a tendency of local recurrence and low risk of distance metastasis. We found it appropriate to submit this case because of its rarity and rapid growth; also, it is the largest size oral cavity location inflammatory myofibroblastic tumor that has been reported so far. [ABSTRACT FROM AUTHOR]

Background: Recently we have generated recombinant human osteopontin (rhOPN) using a plant platform (Nicotiana benthamiana) and demonstrated, when coated on culture plates, its osteogenic induction capacity of human periodontal ligament (PDL) cells. The aim of this study is to elucidate the molecular mechanism underlying the rhOPN-induced osteogenic differentiation of human PDL cells.Methods: Full length rhOPN (FL-OPN) and three constructs of OPN containing integrin binding domain (N142), calcium binding domain (C122) and mutated calcium-binding domain (C122δ) were generated from N. benthamiana. Human PDL cells were isolated from extracted third molars and cultured on FL-OPN, N142, C122, or C122δ-coated surfaces. Real-time PCR and Western blot analyses were used to determine mRNA and protein expression. In vitro calcification was determined by Alizarin red staining. A chemical inhibitor and RNAi silencing were used to elucidate signaling pathways. In silico analyses were performed to predict the protein-protein interaction. In vivo analysis was performed using a rat calvaria defect model.Results: Human PDL cells seeded on FL-OPN and C122-coated surfaces significantly increased both mRNA and protein expression of osterix (OSX) and enhanced in vitro calcification. Soluble FL-OPN as well as a surface coated with N142 did not affect OSX expression. Inhibition of activin receptor-like kinase (ALK-1) abolished the induction of osterix expression. In silico analysis suggested a possible interaction between the calcium binding domain (CaBD) of OPN and ALK-1 receptor. C122, but not C122δ coated surfaces, induced the expression of p-Smad-1 and this induction was inhibited by an ALK-1 inhibitor and RNAi against ALK-1. In vivo data showed that 3D porous scaffold containing C-122 enhanced new bone formation as compared to scaffold alone.Conclusion: The results suggest that next to full length OPN, the CaBD of OPN, if coated to a surface, induces osteogenic differentiation via interaction with ALK-1 receptor. [ABSTRACT FROM AUTHOR]

The uncommon and mysterious pulmonary inflammatory myofibroblastic tumor (PIMT) primarily affects children and young people. PIMT is characterized by the proliferation of myofibroblastic spindle cells mixed with inflammatory cells. It can resemble both benign and malignant disorders, both radiographically and clinically. PIMT typically manifests as a solitary lung tumor. The genesis of the tumor is linked to genetic anomalies, including those related to the ALK gene (anaplastic lymphoma kinase); nonetheless, some cases are not ALK-positive, indicating genetic variability. Clinically, patients may have non-specific symptoms such as cough, chest pain, or hemoptysis, or they may not exhibit any symptoms at all. In these cases, imaging tests may unintentionally reveal unrelated conditions. From a histopathological perspective, PIMT is characterized by a heterogeneous cellular makeup, encompassing lymphocytes, myofibroblasts, plasma cells, and histiocytes, which generally exhibit a fascicular or storiform pattern. The diagnosis is verified using immunohistochemical labeling, molecular research, and histological examination. The cornerstone of treatment is still surgical resection, which has a good prognosis and a low recurrence rate. On the other hand, specific treatments, such as ALK inhibitors, have shown promise for incurable or recurring instances. Even though PIMT usually has a benign history, it is important to comprehend its biological behavior and molecular foundations for precise diagnosis and efficient management. This underscores the need for additional study into the pathophysiology and potential treatments of PIMT. This report presents a case of a 53-year-old female who presented with complaints of breathlessness and chest pain and was diagnosed with the condition accidentally., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bhawani et al.)

Background: Glioblastoma (GB), a grade 4 glioma is the most common primary malignant brain tumor in adults. Recently, the mutation status of isocitrate dehydrogenase (IDH) has been crucial in the treatment of GB. IDH mutant cases display a more favorable prognosis than IDH-wild type ones. The anaplastic lymphoma kinase (ALK) is expressed as a receptor tyrosine kinase in both the developing central and peripheral nervous systems. Increasing lines of evidence suggest that ALK is over-expressed in GB and represents a potential therapeutic target., Objectives: The goal of the current study was to investigate ALK-1 immunohistochemical expression in gliomas, grade 4, besides its correlation with IDH1-R132H mutation status and the clinicopathological parameters of the tumors., Material and Methods: Seventy cases of gliomas, grade 4 were tested for immunohistochemical expression of ALK-1 & IDH1-R132H in the tumor cells., Results: ALK-1 immunoexpression was detected in 22.9% of our cases and IDH1-R132H mutation was detected in 12.9% of them. ALK-1 expression (100%) was only detected in the more aggressive IDH R132H-negative GBs. ALK-1 expression was also noted in the larger-sized tumors, more in males and patients older than the mean age.  Conclusion: Our results suggest that mutations in ALK-1 may predict a more dismal prognosis since ALK expression was only noted in IDH-R132H negative GBs known to have a considerably poorer outcome compared to IDH-R132H mutant cases. GBs with detectable ALK-protein expression could potentially experience substantial clinical advantages through the utilization of newly introduced ALK inhibitors allowing personalized treatment to a subset of patients. Hence, future studies targeting ALK in IDH wildtype Glioblastomas including clinical trials on larger scales are recommended.

Inflammatory myofibroblastic tumors (IMTs) are uncommon tumors that can be classified among fibroinflammatory disorders. IMTs are diagnosed after excluding all other entities, which can be considered differential diagnoses of IMTs. Microscopic examination of IMTs shows multiple myofibroblastic spindle cells, which are surrounded by inflammation. IMTs have lesser chances of progression to malignancy. The case defined below is one of the few cases in the literature that reports the presentation of IMT and another malignancy. We describe a 72-year-old man who was found to have cecal carcinoma and later diagnosed with an IMT of the testis. IMTs are generally benign tumors with a tendency for local recurrence. Patients affected by IMTs usually get diagnosed only after more than one biopsy. IMT is diagnosed only after ruling out other differential diagnoses. They rarely show invasiveness and metastasize. The presence of metastasis, recurrence, and other malignancies probably indicate poor prognosis and poor survival. The course of IMTs is usually benign, with good outcomes after surgery. IMTs have been known to recur, invade, or metastasize in sites such as paranasal sinuses, mediastinum, and the abdomen. In the case that we researched, vimentin and smooth muscle actin were strongly positive in the spindle-shaped cells, whereas anaplastic lymphoma kinase-1 was negative., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chandramouli et al.)