live-cell-imaging-with-time-lapse-photography-to-study-epidermal

Live Cell Imaging with Time Lapse Photography to Study Epidermal Keratinocyte Proliferation Kinetics

Live-cell imaging is an evolving and somewhat challenging method to study keratinocyte behavior in vitro. Historically, keratinocyte division behavior was ...

Memorial Sloan Kettering Cancer Center

Purpose This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. Patients and Methods In total, 189 patients with advanced solid tumors received selinexor (3 to 85 mg/m) in 21- or 28-day cycles. Pre- and post-treatment levels of XPO1 mRNA in patient-derived leukocytes were determined by reverse transcriptase quantitative polymerase chain reaction, and tumor biopsies were examined by immunohistochemistry for changes in markers consistent with XPO1 inhibition. Antitumor response was assessed according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. Results The most common treatment-related adverse events included fatigue (70%), nausea (70%), anorexia (66%), and vomiting (49%), which were generally grade 1 or 2. Most commonly reported grade 3 or 4 toxicities were thrombocytopenia (16%), fatigue (15%), and hyponatremia (13%). Clinically significant major organ or cumulative toxicities were rare. The maximum-tolerated dose was defined at 65 mg/m using a twice-a-week (days 1 and 3) dosing schedule. The recommended phase II dose of 35 mg/m given twice a week was chosen based on better patient tolerability and no demonstrable improvement in radiologic response or disease stabilization compared with higher doses. Pharmacokinetics were dose proportional, with no evidence of drug accumulation. Dose-dependent elevations in XPO1 mRNA in leukocytes were demonstrated up to a dose level of 28 mg/m before plateauing, and paired tumor biopsies showed nuclear accumulation of key tumor-suppressor proteins, reduction of cell proliferation, and induction of apoptosis. Among 157 patients evaluable for response, one complete and six partial responses were observed (n = 7, 4%), with 27 patients (17%) achieving stable disease for ≥ 4 months. Conclusion Selinexor is a novel and safe therapeutic with broad antitumor activity. Further interrogation into this class of therapy is warranted.

First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors.

With the development of immune checkpoint inhibitors, immunotherapy researchers have facilitated substantial progress for patients with mismatch repair deficient/microsatellite instability-high colorectal cancer, which has led to practice changes at a head-spinning pace. However, this benefit has not been translated into microsatellite stable colorectal cancer, which carries the hallmarks of chromosomal instability. So far, clinical trials have not shown any substantial clinical benefits of immune checkpoint inhibitor therapy for patients with microsatellite stable colorectal cancer, which has been disappointing. Recently, combinations of immune checkpoint inhibitors with tyrosine kinase inhibitors and targeted therapies have been investigated for potential synergistic effects that may increase antitumor activity in the tumor microenvironment and achieve more substantial clinical and radiologic responses. In this article, we discuss the current state of the science for the use of immune checkpoint inhibitors in microsatellite stable colorectal cancers, and we review the molecular underpinnings of inherited physiologic barriers for the delivery of effective immunotherapy. We also elaborate on existing therapeutic opportunities to convert microsatellite stable colorectal cancer into an "immune hot" cancer, which may define the future treatment paradigm of colorectal cancer for which there is a great unmet need.

Immunotherapy for Microsatellite Stable Colorectal Cancers: Challenges and Novel Therapeutic Avenues.

Our previous phase II study demonstrated that nivolumab provides modest but durable clinical efficacy in patients with refractory biliary tract cancer, suggesting the significant clinical benefit of nivolumab in selected patients and the necessity of predictive biomarkers. We evaluated clinicopathological characteristics and tumour microenvironment of the patients who were enrolled the trial to identify potential biomarkers.

Biomarker analysis from a phase II multi-institutional study of nivolumab in patients with advanced refractory biliary tract cancer.

Clinical trials suggest α-fetoprotein (AFP) reduction may be prognostic among patients with advanced hepatocellular carcinoma. However, the association of AFP reduction with outcomes in real-world settings is unclear.

Association between posttreatment α-fetoprotein reduction and outcomes in real-world US patients with advanced hepatocellular carcinoma.

Legislative efforts to expand insurance coverage of wigs for individuals with medical causes of alopecia.

Promoting physician diversity is crucial for addressing health care disparities in the United States. Asian Americans and Pacific Islanders (AAPIs) constitute 5.7% of the United States population and 20% of physicians. However, their experiences in cardiothoracic surgery remain underexplored. This work examines historical context, representation, salary data, and AAPIs' personal experiences elaborating on biases and misconceptions faced in academic cardiothoracic surgery.

Article	Year
First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology\| PubMed ID: 26926685	2016
Immunotherapy for Microsatellite Stable Colorectal Cancers: Challenges and Novel Therapeutic Avenues. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting\| PubMed ID: 35658496	2022
Biomarker analysis from a phase II multi-institutional study of nivolumab in patients with advanced refractory biliary tract cancer. European journal of cancer (Oxford, England : 1990)\| PubMed ID: 36252287	2022
Association between posttreatment α-fetoprotein reduction and outcomes in real-world US patients with advanced hepatocellular carcinoma. Cancer\| PubMed ID: 36942492	2023
Legislative efforts to expand insurance coverage of wigs for individuals with medical causes of alopecia. Journal of the American Academy of Dermatology\| PubMed ID: 39561818	2025
From Enigma to Equity: Asian American and Pacific Islanders in Cardiothoracic Surgery. The Annals of thoracic surgery\| PubMed ID: 40054682	2025

Richard Kim

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