Publications by authors named "Kirschner L"

Article Synopsis
  • The study investigates the association between CYP11B2 staining patterns in adrenal tissues and patient outcomes after adrenal surgery in individuals with unilateral primary aldosteronism.
  • A total of 43 patients were reviewed, identifying five distinct CYP11B2 staining patterns, with most cases showing a single adenoma, but also instances of additional staining in nonadenomatous tissues.
  • While the majority of patients achieved biochemical cures, the study found no correlation between CYP11B2 staining patterns and clinical outcomes or demographic factors, highlighting the need for further research to understand these relationships.
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Background: Intraoperative end-tidal carbon dioxide concentrations (EtCO) values are associated with recurrence-free survival after colorectal cancer surgery. However, it is unknown if similar effects can be observed after other surgical procedures. There is now evidence available for target EtCO and its relation to surgical outcomes following pancreatic cancer surgery.

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Article Synopsis
  • Hereditary mutant pheochromocytomas (PC) and paragangliomas (PG) are rare tumors that tend to metastasize unpredictably, prompting a study to better understand their genomic characteristics.
  • A multi-omic analysis of 94 tumors from 79 patients revealed distinct molecular profiles based on whether the tumors originated from sympathetic or parasympathetic cells, with specific alterations linked to metastatic behavior.
  • The study also identified high mutation loads, unusual genomic features, and mechanisms of resistance to DNA alkylating chemotherapies, enhancing the comprehension of these complex neuroendocrine tumors and their treatment responses.
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Study Objective: Higher levels of carbon dioxide (CO) increase the invasive abilities of colon cancer cells in vitro. Studies assessing target values for end-tidal CO concentrations (EtCO) to improve surgical outcome after colorectal cancer surgery are lacking. Therefore, we evaluated whether intraoperative EtCO was associated with differences in recurrence-free survival after elective colorectal cancer (CRC) surgery.

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Importance: Environmental and contextual factors may facilitate or limit participation in daily activities. A detailed, systematic categorization of such factors enhances evaluation and intervention and promotes occupational engagement.

Objective: To develop an inclusive, detailed, and comprehensive typology of terms for environmental and contextual factors that affect occupational engagement and participation.

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Background: Cushing disease represents a challenge for neurosurgeons, with high recurrence rates reported. Characteristics associated with remission are incompletely understood; thus, an intraoperative predictor for outcome would be valuable for assessing resection of adrenocorticotropic hormone (ACTH) secreting tissue.

Objective: To evaluate whether intraoperative ACTH measurement could predict outcome after surgery for Cushing disease.

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Background: The features of long-term remission in acromegaly adenomectomy are incompletely understood. An intraoperative predictor for long-term outcome would be valuable for assessing resection of growth hormone (GH)-secreting tumors in real-time.

Objective: To evaluate whether intraoperative GH measurement could predict long-term outcomes for acromegaly.

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The development of two conventional dendritic cells (DC) subsets (cDC1 and cDC2) and the plasmacytoid DC (pDC) in vivo and in cultures of bone marrow (BM) cells is mediated by the growth factor Flt3L. However, little is known about the factors that direct the development of the individual DC subsets. Here, we describe the selective in vitro generation of murine ESAM CD103 XCR1 CD172a CD11b cDC2 from BM by treatment with a combination of Flt3L, LIF, and IL-10 (collectively named as FL10).

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Several new -substituted 1,2-benzisothiazol-3(2)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties.

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: Adrenocortical cancer (ACC) is a rare and aggressive disease with a median survival of 14-17 months and 5-year survival of around 20% for advanced disease. Emerging evidence of sub-groups of ACC with specific molecular drivers indicate ACC may be amenable to inhibition of receptor tyrosine kinases involved in growth and angiogenic signaling. A significant subset of patients may also be responsive to immune strategies.

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To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications "off-label" against SARS-CoV-2. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.

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Article Synopsis
  • Hereditary endocrine tumor syndromes are rare but complex conditions that require careful differentiation by healthcare providers for effective treatment.
  • A genetic counselor specialized in endocrine cancer genetics was added to a clinic at The Ohio State University, seeing a total of 358 patients mainly referred by medical oncology.
  • Genetic testing revealed that 15.5% of patients had likely pathogenic or pathogenic variants, with particular genes showing higher occurrences, which may guide future patient care and the establishment of similar clinics.
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Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections.

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Protein kinase A (PKA) activity is pivotal for proper functioning of the human heart, and its dysregulation has been implicated in a variety of cardiac pathologies. PKA regulatory subunit 1α (R1α, encoded by the PRKAR1A gene) is highly expressed in the heart, and controls PKA kinase activity by sequestering PKA catalytic subunits. Patients with PRKAR1A mutations are often diagnosed with Carney complex (CNC) in early adulthood, and may die later in life from cardiac complications such as heart failure.

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Thyroid cancer affects about one percent of the population, and has seen rising incidence in recent years. Follicular thyroid cancer (FTC) comprises 10-15% of all thyroid cancers. Although FTC is often localized, it can behave aggressively with hematogenous metastasis, leading to an increased risk of cancer death.

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Adrenocortical carcinoma (ACC) is a rare malignancy with limited data to guide the management of metastatic disease. The optimal treatment strategies and outcomes of patients with metastatic ACC remain areas of active interest. We retrospectively reviewed patients with ACC who were treated with systemic therapy between January 1997 and October 2016 at The Ohio State University Comprehensive Cancer Center.

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Context: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab.

Objective: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors.

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Context: Although important advances have been made in understanding the genetics of endocrine tumors, cellular physiology is relatively understudied as a determinant of tumor behavior. Oxidative stress and reactive oxygen species are metabolic factors that may affect tumor behavior, and these are, in part, controlled by manganese-dependent superoxide dismutase (MnSod), the mitochondrial superoxide dismutase (encoded by SOD2).

Objective: We sought to understand the role of MnSod in the prognosis of aggressive human endocrine cancers and directly assessed the effect of MnSod under- or overexpression on tumor behavior, using established mouse thyroid cancer models.

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Context: The development of diabetes insipidus (DI) following transsphenoidal resection of pituitary adenomas has been associated with higher postsurgical morbidity and longer hospitalizations. Identifying these patients promptly and efficiently can lead to improved health care outcomes.

Objective: We evaluated our institution's incidence of DI following pituitary adenoma resection and assessed for preoperative risk factors that were associated with postoperative DI.

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Background: Thyroid cancer is an emerging health problem in the United States and worldwide. With incidence rates of thyroid cancer rapidly rising, the need to develop new treatment options is becoming a priority, and understanding the molecular mechanisms of this disease is crucial to furthering these efforts. Thyroid growth is driven by the TSH/cAMP/PKA signaling pathway, and it has previously been shown that activation of PKA through genetic ablation of the regulatory subunit Prkar1a (Prkar1a KO) is sufficient to cause follicular thyroid cancer in mouse models.

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Alterations in circulating thyroid hormone concentrations are associated with several psychological and behavioral disorders. In humans, behavioral disorders such as anxiety, depression, and attention-deficit hyperactivity disorder can be associated with thyroid disease. The Tpo-Cre;Prkar1a;Epac1 (R1A-Epac1KO) mice, originally bred to investigate the role of exchange protein directly activated by cAMP (Epac1) in follicular thyroid cancer, displayed self-mutilating and aggressive behaviors during casual observation.

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