Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer.

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin β4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling.

Erratum: A Non-genetic Mechanism Involving the Integrin β4/Paxillin Axis Contributes to Chemoresistance in Lung Cancer.

[This corrects the article DOI: 10.1016/j.isci.

The O-Linked N-Acetylglucosamine Containing Epitope H (O-GlcNAcH) is Upregulated in the Trophoblastic and Downregulated in the Fibroblastic Cells in Missed Miscarriage Human Chorionic Villi With Simple Hydropic Degeneration.

Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAcH) residue in a specific conformation and/or environment recognized by the mouse monoclonal antibody H. O-GlcNAcH is present in several types of cells and in several polypeptides, including cytokeratin 8 and vimentin, on the latter in cells under stress. In the present work, we examined the expression of the O-GlcNAcH in 60 cases of endometrial curettings from missed miscarriage cases containing normal and simple hydropic degenerated chorionic villi in each case, using monoclonal antibody H and indirect immunoperoxidase and Western blot immunoblot.

Alternative lengthening of telomeres, ATRX loss and H3-K27M mutations in histologically defined pilocytic astrocytoma with anaplasia.

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fifty-seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3-75) were included. A clinical diagnosis of NF1 was present in 8 (22%).

Glioblastoma in natalizumab-treated multiple sclerosis patients.

We present two natalizumab-treated multiple sclerosis patients who developed glioblastoma multiforme (GBM) with variable outcomes. One patient had an isocitrate dehydrogenase (IDH)-wildtype GBM with aggressive behavior, who declined treatment and died 13 weeks after symptoms onset. The other patient underwent resection of an IDH-mutant secondary GBM that arose from a previously diagnosed grade II astrocytoma.

Pigmented ganglioglioma in a patient with chronic epilepsy and cortical dysplasia.

We report a rare case of a 22-year-old woman with biopsy-proven pigmented ganglioglioma. The patient initially underwent a right temporal lobectomy for intractable seizures at the age of 9 and remained seizure free for several years but subsequently developed complex partial seizures. Due to enhancement of a left mesial occipital lesion on preoperative MRI of the brain, the patient underwent a left subdural electrode placement and simultaneous biopsy of the left mesial occipital lesion.

Hyperdense suprasellar mass: An unusual radiological presentation of intracranial dermoid cyst.

We report an exceedingly rare patient with a hyperdense suprasellar dermoid cyst and a pertinent review of the literature. Intracranial dermoid tumors are rare congenital lesions of the brain that account for less than 1% of all intracranial tumors. Even though they are rare, typical CT scan and MRI features and location allow radiological diagnosis in the majority of patients.

A 40-year-old male with an intraventricular tumor. Combined tanycytic ependymoma and subependymoma.

Combined tumors showing histologic features of both ependymoma and subependymoma have been described. In this report we present a case of combined tanycytic ependymoma with foci of subependymoma (WHO grade II), occurring in a 40 year-old male, which arose in the wall of the lateral ventricle. The tanycytic ependymoma component showed elongated fibrillary cells with a fascicular pattern of growth, while the subependymoma component showed clustered cell bodies surrounded by a fibrillary stroma with a microcystic appearance.

Immunophenotype of myxopapillary ependymomas.

Myxopapillary ependymoma (MPE) is a slow-growing tumor occurring almost exclusively in the region of conus medullaris, cauda equina, and filum terminale. On microscopic examination, some of these tumors show solid sheets of cells with an epithelioid morphology mimicking a metastatic carcinoma. Several immunohistochemical studies addressed this issue with discordant results.

Use of the reamer-irrigator-aspirator may reduce tumor dissemination during intramedullary fixation of malignancies.

Intramedullary nail fixation is the treatment of choice for impending and pathologic fractures secondary to metastatic cancer; however, this procedure has been shown to cause systemic embolization of intramedullary contents. This article reports the use of the reamer-irrigator-aspirator (RIA) (Synthes, Paoli, Pennsylvania) instead of a standard femoral reamer to decrease tumor intravasation during femoral intramedullary nail fixation for impending or pathologic fractures.Twenty-one consecutive patients indicated for fixation of malignant femoral lesions were treated with intramedullary nail placement.

Hypoxia upregulates the expression of the O-linked N-acetylglucosamine containing epitope H in human ependymal cells.

Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a specific conformation and/or environment recognized by mouse IgM monoclonal antibody H (mabH). Epitope H is present in several types of cells and in several polypeptides outside the CNS. Previous results have shown that in the adult human brains, epitope H is confined mostly to a minority of fibrous astrocytes, and it is greatly upregulated in the reactive astrocytes.

Prognostic value of xanthine oxidoreductase expression in patients with non-small cell lung cancer.

Background: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the purine metabolism pathway. Lack of XOR expression is associated with unfavorable clinical outcomes. The objective of this study was to correlate XOR expression with prognosis in surgically resected non-small cell lung cancer (NSCLC).

Melanotic schwannoma: a case with strong CD34 expression, with histogenetic implications.

Melanotic schwannomas (MS) are rare tumors composed of cells with both schwannian and melanocytic features, which usually occur in the setting of Carney's Complex. We describe a case of a 36-year-old male who presented with a mass that was attached to the vertebral body as well as the nerve roots of L2 and L3. Immunohistochemical positivity for S-100, HMB-45, and Pan-melanoma markers, as well as characteristic morphologic and ultrastructural findings, suggested that the lesion was a MS.

Congenital fusion of the thalami (atresia of the third ventricle) associated with parietooccipital meningocele.

In this article we present a case of a male newborn with a CNS malformation that is characterized mainly by complete fusion of the thalami resulting in atresia of the 3rd ventricle accompanied by fusion of the anterior peduncles of the fornix, the presence of a single occult interventricular foramen lying at the midline, absence of the septum pellucidum, hypoplasia of the corpus callosum, disorganization of the head of the left caudate nucleus, and greatly dilated lateral ventricles (hydrocephalus). The patient underwent surgical correction of the meningocele on his 4th postnatal day. On his 13th postnatal day he had projectile vomiting due to a left parietooccipital hygroma that was drained via a shunt.

Adrenocortical carcinoma presenting with a peritoneal effusion.

In this report, we describe the fine-needle aspiration findings of a case of adrenocortical carcinoma (ACC) that spread to the peritoneal cavity in an 80-year-old female. Cytologically, the peritoneal fluid exhibited clusters and single, small uniform cells with round nuclei and a fine chromatin pattern, which in conjunction with the immunohistochemical stains was diagnostic of ACC. Although ACC is the most common malignant neoplasm of the adrenal gland, its metastatic spread to the peritoneal cavity is exceptionally unusual.

The expression of the O-linked N-acetylglucosamine containing epitope H in the gemistocytic, pilocytic and subependymal giant cell astrocytomas.

The epitope H contains an O-linked N-acetylglucosamine residue in a specific conformation and/or environment recognized by the monoclonal antibody H. It has previously been shown that the epitope H is present in several types of normal and pathological cells and in several polypeptides. In normal human brains the epitope H is present mostly to a minority of fibrous astrocytes, whereas it is greatly up-regulated in reactive astrocytes and is increased in well differentiated fibrillary astrocytomas compared to anaplastic astrocytomas and glioblastomas.

Altered expression pattern of integrin alphavbeta3 correlates with actin cytoskeleton in primary cultures of human breast cancer.

Background: Integrins are transmembrane adhesion receptors that provide the physical link between the actin cytoskeleton and the extracellular matrix. It has been well established that integrins play a major role in various cancer stages, such as tumor growth, progression, invasion and metastasis. In breast cancer, integrin alphavbeta3 has been associated with high malignant potential in cancer cells, signaling the onset of widespread metastasis.

Expression of the O-linked N-acetylglucosamine containing epitope H in normal myometrium and uterine smooth muscle cell tumors.

Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a specific conformation and/or environment recognized by monoclonal antibody H (mAbH). We have previously shown that epitope H is present in more than one polypeptide and in various types of normal and pathological cells. In the present study, we focused on uterine smooth muscle cell tumors and their adjacent normal myometrium to gain further insight into the expression patterns of epitope H in human tissues.

Nuclear localization of cytokeratin 8 and the O-linked N-acetylglucosamine-containing epitope H in epithelial cells of infiltrating ductal breast carcinomas: a combination of immunogold and EDTA regressive staining methods.

In a previous study, the authors have shown cytokeratin 8 (CK8) and epitope H ultrastructural localization in breast cancer cell nuclei. Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a specific conformation and/or environment recognized by monoclonal antibody H. In this study, double immunogold labeling of CK8 and epitope H combined with the EDTA regressive staining method was applied in biopsy material from infiltrating ductal breast carcinomas and fibroadenomas, to localize both antigens in correlation to RNPs distribution in the nuclear subcompartments of cancer cells.

Mitochondria-rich normal, metaplastic, and neoplastic cells show overexpression of the epitope H recognized by the monoclonal antibody H.

The epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a specific conformation and/or environment recognized by monoclonal antibody H (mAbH). We have previously shown that the epitope H is present in more than one polypeptide and in various types of normal and pathological cells. In the present study, we focused on mitochondria-rich normal, metaplastic, and neoplastic cells, prompted by our recent immuno-electron microscopy findings that mAbH clearly stains the mitochondria of breast epithelial cells in infiltrating ductal breast carcinomas and fibroadenomas.