T-Cell Malignant Neoplasms After Chimeric Antigen Receptor T-Cell Therapy.

This cohort study assesses the increase in second primary malignant neoplasms and T-cell malignant neoplasm cases associated with chimeric antigen receptor­T cells.

Cutaneous Hypersensitivity Reactions to Immune Checkpoint Inhibitors.

The introduction of immune checkpoint inhibitors (ICIs) has transformed the management of various malignancies. Alongside their therapeutic success, the widespread application of ICIs has unveiled a spectrum of immune-related adverse events (irAEs), most often affecting the skin. Cutaneous irAEs (cirAEs) encompass a range from common morbilliform and lichenoid rashes to more severe conditions such as bullous dermatoses and psoriasiform eruptions, each presenting distinct clinical challenges. Moreover, less common but clinically severe cutaneous reactions like toxic epidermal necrolysis have also been observed. cirAEs are frequently observed, with an incidence ranging from 37% to 70% for anti-cytotoxic T lymphocyte-associated antigen-4 antibodies and 17% to 40% for anti- programmed death-1/anti-programmed death ligand-1 antibodies. Recognizing the critical need for effective therapeutic strategies, this review carefully examines current approaches and guidelines for managing cirAEs.

Efficacy and Tolerability of HydraFacial Clarifying Treatment Series in the Treatment of Active Acne Vulgaris.

Objective: This 12-week, multicenter, open-label study investigated the efficacy and tolerability of the HydraFacial Clarifying Treatment for improving skin appearance in patients who present with acne vulgaris. Methods: Twenty eligible adult patients with mild-to-moderate acne were enrolled at one of two treatment sites in the United States and were to undergo six HydraFacial Clarifying Treatments, one every two weeks for 12 weeks. Treatment occurs in three steps: cleansing and peeling; suction to extract dead skin cells, sebum, and debris; and application of blue LED light. Acne severity was graded by investigators and by patients using the Global Acne Severity Score (GASS). Results: The proportion of patients with no acne or almost clear skin (GASS ≤1) at baseline versus final treatment increased from 20 to 65 percent per investigator assessment (p=0.0027), and from 5 to 55 percent per patient self-report (p=0.0016). At final treatment, more than 80 to 100 percent of both investigators and patients agreed or strongly agreed there was an improvement in skin appearance across multiple assessment parameters. Treatments were generally well tolerated. Limitations: Due to the nature of the treatment, blinding of neither investigators nor patients was feasible. Conclusion: The results presented here suggest that a series of six HydraFacial Clarifying Treatments improves overall skin appearance in patients with active acne.

Platelet-Coated Circulating Tumor Cells Are a Predictive Biomarker in Patients with Metastatic Castrate-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) includes a subset of patients with particularly unfavorable prognosis characterized by combined defects in at least two of three tumor suppressor genes: PTEN, RB1, and TP53 as aggressive variant prostate cancer molecular signature (AVPC-MS). We aimed to identify circulating tumor cells (CTC) signatures that could inform treatment decisions of patients with mCRPC with cabazitaxel-carboplatin combination therapy versus cabazitaxel alone. Liquid biopsy samples were collected prospectively from 79 patients for retrospective analysis. CTCs were detected, classified, enumerated through a computational pipeline followed by manual curation, and subjected to single-cell genome-wide copy-number profiling for AVPC-MS detection. On the basis of immunofluorescence intensities, detected rare cells were classified into 8 rare-cell groups. Further morphologic characterization categorized CTC subtypes from 4 cytokeratin-positive rare-cell groups, utilizing presence of mesenchymal features and platelet attachment. Of 79 cases, 77 (97.5%) had CTCs, 24 (30.4%) were positive for platelet-coated CTCs (pc.CTCs) and 25 (38.5%) of 65 sequenced patients exhibited AVPC-MS in CTCs. Survival analysis indicated that the presence of pc.CTCs identified the subset of patients who were AVPC-MS-positive with the worst prognosis and minimal benefit from combination therapy. In AVPC-MS-negative patients, its presence showed significant survival improvement from combination therapy. Our findings suggest the presence of pc.CTCs as a predictive biomarker to further stratify AVPC subsets with the worst prognosis and the most significant benefit of additional platinum therapy. IMPLICATIONS: HDSCA3.0 can be performed with rare cell detection, categorization, and genomic characterization for pc.CTC identification and AVPC-MS detection as a potential predictive biomarker of mCRPC.

Nelfinavir is effective against human cervical cancer cells in vivo: a potential treatment modality in resource-limited settings.

OBJECTIVE: The standard treatment for cervical cancer in developed countries includes surgery and chemoradiation, with standard of care lagging in developing countries. Even in the former case, treatment frequently yields recalcitrant tumors and women succumb to disease. Here we examine the impact of nelfinavir, an off-patent viral protease inhibitor, which has shown promise as an antineoplastic agent. METHODS: We evaluated the morphological and proliferative effects of the autophagy-stressing drug nelfinavir in normal and cisplatin-resistant cervical cancer cells. Immunofluorescent validation of autophagy markers was performed and the impact of nelfinavir in an in vivo model of tumor growth was determined. RESULTS: Nelfinavir exhibits cytotoxicity against both cisplatin-sensitive and -resistant ME-180 human cervical cancer cells in vitro and in vivo. Immunoblotting and immunofluorescence showed an expression of the autophagy marker LC3-II in response to nelfinavir treatment. CONCLUSION: Nelfinavir, now available as an inexpensive generic orally dosed agent (Nelvir), is cytotoxic against cervical cancer cells. It acts by burdening the autophagy pathway to impair tumor cell survival and a modest induction of apoptosis. While further studies are needed to elucidate the optimal method of application of nelfinavir, it may represent an appealing global option for the treatment of cervical cancer.