Roswell Park Comprehensive Cancer Center is a cancer research and treatment center located in Buffalo, New York. Founded by Roswell Park in 1898, the center was the first in the United States to specifically focus on cancer research. The center, which conducts clinical research on cancer as well as the development new drugs, provides advanced treatment for all forms of adult and pediatric cancer, and serves as a member of the National Comprehensive Cancer Network. Roswell Park Comprehensive Cancer Center is currently the only upstate New York facility to hold the National Cancer Institute designation of "comprehensive cancer center".The Roswell Park campus, spread out in 15 separate buildings of approximately two million square feet, occupies 28 acres (11 ha) on the 100-acre (40 ha) Buffalo Niagara Medical Campus (BNMC) in downtown Buffalo, and includes 1,500,000 square feet (140,000 m2) of space equally distributed between clinical programs and research/education functions. A separate hospital building, completed in 1998, houses a diagnostic and treatment center. The campus also includes a medical research complex as well as research and education focused spaces.
Objective This study updates a previous paper that examined trends in the sale of cigarettes and heated tobacco products (HTPs) in Japan between 2011 and part way through 2019. The current study includes complete unit sales data through 2023.Methods Data on cigarette and HTP sales were obtained from public sources available from the websites and stockholder reports for the Tobacco Institute of Japan, Philip Morris International and Japan Tobacco. We used joinpoint regression using the parametric method to test for trends in both per capita and total sales for the three outcome variables assessed between 2011 and 2023: (1) cigarette sales, (2) HTP sales and (3) combined cigarette and HTP sales. Joinpoint regression identifies changes in trends and estimates the annual per cent change (APC) for each trend segment.Results Between 2011 and 2023, per capita and total cigarette sales declined by 52.6% and 52.7%, respectively. From 2011 to 2015, per capita cigarette sales in Japan decreased -1.5% APC; from 2015 to 2018, the decline accelerated to -10.5% APC and continued to fall -7.3% APC between 2018 and 2023. Between 2016 and 2018, per capita HTP sales increased by 149.0% APC, and since 2018, they have increased by 8.1% APC.Conclusion While many factors may account for the decreased sale of cigarettes in Japan over the past 12 years, the increased sale of HTPs appears to be a factor.
Chromosomal instability (CIN) and epigenetic reprogramming are central drivers of breast cancer progression, yet the mechanisms connecting them remain elusive. Here, we uncover a direct role for EZH2 histone methyltransferase in promoting CIN in triple-negative breast cancer. Across breast cancers, EZH2 expression correlates with copy-number alterations, and its catalytic activity is associated with increased CIN in metastasis-initiating cells. Pharmacologic EZH2 inhibition suppresses CIN, revealing an unexpected vulnerability. Integrated chromatin and transcriptome profiling identified tankyrase (TNKS), a PARP, as a direct transcriptional target of EZH2. Mechanistically, EZH2-mediated TNKS suppression disrupts centrosomal P4.1-associated protein (CPAP), driving centrosome overduplication, multipolar mitosis, and exacerbated CIN. In vivo, CIN suppression is a critical mechanism underlying the antimetastatic effects of EZH2 inhibition. These findings delineate a previously unrecognized epigenetic mechanism governing CIN and establish EZH2 inhibitors as the first therapeutic agents capable of directly suppressing CIN, underscoring the need for trials with metastasis-focused endpoints. SIGNIFICANCE:We elucidate epigenetic regulation of CIN through EZH2-TNKS-CPAP-axis and show that CIN suppression is important for the efficacy of EZH2 inhibition on metastasis. These mechanistic insights are informative for developing CIN-suppressing therapies.
BACKGROUND:Nivolumab plus ipilimumab (NIVO + IPI) demonstrated significant long-term survival and response benefits in patients with previously untreated advanced renal cell carcinoma (aRCC) in the phase III CheckMate 214 trial (NCT02231749). We report final efficacy and safety results with 9.3 years median follow-up. PATIENTS AND METHODS:Patients (N = 1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks × four doses, followed by NIVO (3 mg/kg or 240 mg every 2 weeks or 480 mg every 4 weeks); or sunitinib (SUN) (50 mg) once daily (4 weeks on, 2 weeks off). ENDPOINTS:overall survival (OS), and independent radiology review committee-assessed progression-free survival and objective response rate in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk (primary), intention-to-treat (secondary), and IMDC favorable-risk (exploratory) patients. RESULTS:With a median (range) follow-up of 9.3 years (8.6-9.9 years), the hazard ratio (95% confidence interval) for OS with NIVO + IPI versus SUN was 0.71 (0.62-0.82) in intention-to-treat patients, 0.69 (0.59-0.81) in intermediate/poor-risk patients, and 0.80 (0.59-1.09) in favorable-risk patients; 108-month OS probabilities were 31.4% versus 19.5%, 30.2% versus 18.7%, and 35.3% versus 21.8%, respectively. Progression-free survival probabilities at 96 months were 22.7% versus 9.0% (intention-to-treat), 25.4% versus 8.5% (intermediate/poor risk), and 12.5% versus 11.3% (favorable risk). Probabilities of remaining in response at 96 months with NIVO + IPI versus SUN were 48.0% versus 19.0% (intention-to-treat), 50.0% versus 23.0% (intermediate/poor risk), and 36.0% versus not estimable (favorable risk). Incidence of any-grade (grade 3-4) treatment-related adverse events (AEs) was 94.1% (48.6%) with NIVO + IPI versus 97.6% (64.1%) with SUN. Exploratory post hoc analyses reported include descriptive analyses of OS by immune-mediated AE discontinuation status. CONCLUSIONS:In the longest phase III follow-up of a first-line checkpoint inhibitor combination in aRCC (>9 years), NIVO + IPI maintained a substantial survival benefit with durable responses versus SUN. Grade 3-4 treatment-related AEs were lower with NIVO + IPI versus SUN at 9 years. NIVO + IPI remains a first-line standard of care in aRCC.
BACKGROUND:Various poly(ADP-ribose) polymerases (PARPs) are known to be related to DNA repair, and PARP7 has been linked to estrogen signaling and immunity. Recently, PARP7 was shown to increase cancer cell proliferation, but reports are conflicting. Given that these studies are mostly based on in vitro experiments, this study investigated how PARP7 expression impacts breast cancer patients. METHODS:Clinical and transcriptomic data of breast cancer patients were obtained from the METABRIC (n = 1904), TCGA (n = 1090), and SCAN-B (n = 3069) cohorts. The median value was used to divide the cohorts into high- and low-PARP7 groups. RESULTS:High PARP7 expression was significantly associated with better overall survival in two of the three cohorts (p < 0.05), and PARP7 was expressed predominantly by epithelial cells (p < 0.001). Estrogen receptor (ER)-positive breast cancer had a higher expression of PARP7 than other subtypes (p < 0.001). High PARP7 expression was associated with high estrogen and androgen response consistently in all cohorts. Tumors expressing higher PARP7 levels had significantly lower mutation rates, neoantigens, type 1 interferon (IFN-1), and immune cell infiltration in (p < 0.001). High PARP7 expression was associated with less enrichment of cell proliferation-related gene sets (E2F targets, G2M checkpoint, and MYC targets), in all cohorts. Higher PARP7 expression was associated with less cancer cell proliferation, lower tumor grade, and lower Ki67 (p < 0.001). CONCLUSION:High PARP7 expression is associated with estrogen and androgen response, but also with better overall survival and lower cell proliferation.
Aromatherapy holds promise for reducing chemotherapy-related symptoms, however, lacks robust clinical evidence. This study evaluates the feasibility and benefit of aromatherapy in managing chemotherapy-related symptoms. This four-arm, randomized, blinded clinical trial enrolled 91 cancer patients (≥ 8 years) undergoing chemotherapy for cancer. Participants were randomized into one of four arms (lavender, jojoba, orange, and ginger) for two chemotherapy cycles (Baseline—no aromatherapy and Cycle 2 – aromatherapy) with an optional third cycle. Participants used aromatherapy inhalers at least 4 times/day for 7 days and rated severity of 7 symptoms (i.e., nausea, vomiting, pain, anxiety, fatigue, sleep difficulties, and lack of appetite) from 0 to 10 daily during each cycle. Primary outcome was feasibility (i.e., retention and aromatherapy compliance through Cycle 2). Preliminary efficacy was evaluated using mean composite symptom severity scores (CSSS; sum daily scores of all individual symptoms for the seven days per cycle). Of the 91 participants randomized, 84 participants started Baseline with 68 completing through Cycle 2. Aromatherapy demonstrated feasibility with overall retention rate of 81.0
