Superconducting qubits probe environmental defects such as nonequilibrium quasiparticles, an important source of decoherence. We show that "hot" nonequilibrium quasiparticles, with energies above the ...superconducting gap, affect qubits differently from quasiparticles at the gap, implying qubits can probe the dynamic quasiparticle energy distribution. For hot quasiparticles, we predict a non-negligible increase in the qubit excited state probability Pe. By injecting hot quasiparticles into a qubit, we experimentally measure an increase of Pe in semiquantitative agreement with the model and rule out the typically assumed thermal distribution.
Background
Prognosis in pancreatic ductal adenocarcinoma (PDAC) remains poor despite improved systemic therapies and surgical techniques. The identification of biomarkers to advance insight in tumor ...biology and achieve better individualized prognostication could help improve outcomes. Our aim was to elucidate the prognostic role of the four main driver mutations (
KRAS
,
TP53
,
SMAD4
,
CDKN2A
) and their combinations in resected PDAC.
Patients and Methods
A retrospective analysis was conducted utilizing the cBioPortal database and National Cancer Institute’s Cancer Genomic Atlas (TCGA) on patients in whom next-generation sequencing was performed on upfront resected PDAC from 2012 to 2020. Multivariable Cox regression was implemented to elucidate risk-adjusted predictors of overall (OS) and recurrence-free survival (RFS). Results were validated employing a Johns Hopkins Hospital (JHH) cohort.’
Results
In the discovery cohort (
n
= 587), increased number of mutated driver genes was associated with worse OS (
p =
0.047). Specifically, patients with mutations in ≥ 2 driver genes had worse OS than ≤ 1 mutated gene (18.2 versus 32.3 months,
p =
0.033). Co-occurrence of mutant (mt)
KRAS
p
.
G12D with mt
TP53
(median OS, 25.9 months) conferred better prognosis than co-occurrence of other mt
KRAS
variants (p.G12V/R/other) with mt
TP53
(median OS, 16.9 months,
p =
0.038). The findings were validated using a JHH cohort. Multivariable risk-adjustment found co-occurrence of mt
KRAS
p.G12D with mt
TP53
to be an independent predictor of beneficial OS and RFS HR (95% CI): 0.18 (0.03–0.81) and 0.31 (0.11–0.89) respectively.
Conclusion
In chemo-naïve resected PDAC, combinations of mutations in the four driver genes are associated with prognosis. In patients with combined mt
KRAS
and mt
TP53
,
KRAS
p.G12D variant confers a better OS and RFS.
Abstract
Nasopharyngeal carcinoma (NPC) is caused by Epstein-Barr virus (EBV) and is more likely to occur in susceptible families. Whether genetic susceptibility operates through altered EBV control ...is incompletely understood. We used a NPC risk prediction model based on 14 EBV markers to compare risk score distribution in unaffected members from multiplex families with that in population-based controls. Despite the absence of NPC at the time of antibody measurement, we observed an upward shift in risk score among multiplex family members compared to the general population, consistent with the possibility that genetic factors affect NPC risk through alterations in EBV control.
A previous cancer diagnosis is a negative consideration in evaluating patients for possible solid organ transplantation. Statistical models may improve selection of patients with cancer evaluated for ...transplantation.
We fitted statistical cure models for patients with cancer in the US general population using data from 13 cancer registries. Patients subsequently undergoing solid organ transplantation were identified through the Scientific Registry of Transplant Recipients. We estimated cure probabilities at diagnosis (for all patients with cancer) and transplantation (transplanted patients). We used Cox regression to assess associations of cure probability at transplantation with subsequent cancer-specific mortality.
Among 10,524,326 patients with 17 cancer types in the general population, the median cure probability at diagnosis was 62%. Of these patients, 5,425 (0.05%) subsequently underwent solid organ transplantation and their median cure probability at transplantation was 94% (interquartile range, 86%-98%). Compared with the tertile of transplanted patients with highest cure probability, those in the lowest tertile more frequently had lung or breast cancers and less frequently colorectal, testicular, or thyroid cancers; more frequently had advanced-stage cancer; were older (median 57
51 years); and were transplanted sooner after cancer diagnosis (median 3.6
8.6 years). Patients in the low-cure probability tertile had increased cancer-specific mortality after transplantation (adjusted hazard ratio, 2.08; 95% CI, 1.48 to 2.93;
the high tertile), whereas those in the middle tertile did not differ.
Patients with cancer who underwent solid organ transplantation exhibited high cure probabilities, reflecting selection on the basis of existing guidelines and clinical judgment. Nonetheless, there was a range of cure probabilities among transplanted patients and low probability predicted increased cancer-specific mortality after transplantation. Cure probabilities may facilitate guideline development and evaluating individual patients for transplantation.
Males have 2-3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex ...differences remained among immunocompromised adults.
Using the Transplant Cancer Match (TCM) study, we estimated the male-to-female incidence rate ratio in TCM (M:F IRRTransplant) for 15 cancer sites diagnosed between 1995 and 2017 using Poisson regression. Male to female IRRs in the general population (M:F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race and ethnicity, and diagnosis year. Male to female IRRs were compared using a chi-square test.
Among 343 802 solid organ transplants, 211 206 (61.4%) were among men and 132 596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M:F IRRTransplant: 1.81 vs M:F IRRGP: 3.96; P < .0001), stomach (1.51 vs 2.09; P = .002), colorectum (0.98 vs 1.43; P < .0001), liver (2.39 vs 3.44; P = .002), kidney (1.67 vs 2.24; P < .0001), bladder (2.02 vs 4.19; P < .0001), Kaposi sarcoma (1.79 vs 3.26; P = .0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P < .0001). The M:F IRRTransplant was not statistically different from the M:F IRRGP for other cancer sites.
Although male solid organ transplant recipients have higher cancer incidence than female recipients, the attenuation in the male to female ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in female recipients due to immunosuppression after transplantation.
IMPORTANCE: Nonkeratinocyte skin cancers are an important cause of morbidity and mortality for immunosuppressed solid organ transplant recipients (SOTRs), but the spectrum of disease and risk factor ...characteristics are unknown. OBJECTIVE: To characterize the spectrum of disease and risk factors for common and rare nonkeratinocyte skin cancers in SOTRs. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included 444 497 SOTRs who underwent a transplant in the US between January 1, 1987, and December 31, 2017, using linked data from the national transplant registry and 32 cancer registries. Data analysis was conducted from April 1, 2021, to September 30, 2021. MAIN OUTCOMES AND MEASURES: Standardized incidence ratios (SIRs) were used to assess risk relative to the general population, and Poisson regression was used to evaluate risk factors. RESULTS: A total of 2380 nonkeratinocyte skin cancers were identified among 444 497 SOTRs (median age at transplant, 50 years; range, 0-96 years; 274 276 61.7% male; 272 241 61.2% non-Hispanic White). Melanoma was the most common cancer (1471 61.8%), followed by Merkel cell carcinoma (334 14.0%), Kaposi sarcoma (186 7.8%), sebaceous carcinoma (170 7.1%), and cutaneous lymphomas (108 4.5%). Risks were most strongly elevated for cancers associated with viruses, including Kaposi sarcoma (SIR, 20.5; 95% CI, 17.7-23.7), Merkel cell carcinoma (SIR, 16.2; 95% CI, 14.5-18.1), and extranodal natural killer/T-cell lymphoma (SIR, 44.3; 95% CI, 5.37-160). Risks were also significantly elevated for sebaceous carcinoma (SIR, 15.2; 95% CI, 13.0-17.7), anaplastic large cell lymphoma (SIR, 6.82; 95% CI, 4.53-9.85), and diffuse large B-cell lymphoma (SIR, 5.17; 95% CI, 3.28-7.76). Several characteristics were independently associated with greater risk for multiple skin cancer types, including male sex, older age at transplant, factors associated with UV radiation exposure (non-Hispanic White race and ethnicity, living in an area with higher UV radiation exposure, and posttransplant diagnosis of keratinocyte carcinoma), and increasing time since transplantation. Treatment with mammalian target of rapamycin inhibitors was associated with reduced melanoma incidence (incidence rate ratio, 0.75; 95% CI, 0.57-0.98). A total of 847 skin cancers (39.4%) occurred on the head and neck. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that viruses, UV radiation exposure, and immunosuppression are associated with the development of skin cancer in SOTRs. Certain high-risk subgroups may benefit from increased skin surveillance, and treatment with mammalian target of rapamycin inhibitors could be effective for melanoma chemoprevention in the transplant population.
Melanoma causes significant morbidity in solid organ transplant recipients (SOTRs). Melanomas diagnosed before transplantation can recur with intensive immunosuppression, but outcomes have not been ...well studied. We evaluated 901 non-Hispanic White SOTRs with a pretransplant melanoma identified using linked transplant and cancer registry data in the United States. Most pretransplant melanomas were invasive (60.7%), and the median time from diagnosis to transplantation was 5.1 years. After transplantation, 41 SOTRs developed a new invasive melanoma, corresponding to 9-fold increased risk compared with the general population (standardized incidence ratio, 9.2; 95% confidence interval CI, 6.6-12). Twenty-two SOTRs died from melanoma after transplantation, corresponding to 52-fold increased risk (standardized mortality ratio, 52; 95% CI, 33-79). Risk factors for posttransplant melanoma included age at transplantation (adjusted hazard ratio HR, 2.86; 95% CI, 1.24-6.60; for age 55+ vs <55 years) and maintenance immunosuppression with cyclosporine/azathioprine (adjusted HR, 2.53; 95% CI, 1.08-5.90). Melanoma mortality was strongly elevated after a posttransplant melanoma diagnosis (HR, 35.6; 95% CI, 14.0-90.4; adjusted for cyclosporine/azathioprine maintenance therapy and calendar year of transplantation). In conclusion, SOTRs with a pretransplant melanoma are at risk of adverse melanoma-related outcomes after transplantation. These findings support thorough dermatologic evaluation prior to transplantation and frequent posttransplant surveillance.
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Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are ...estrogen receptor alpha positive (ERα+) and represent risk indicators and/or precursor lesions to low grade ERα+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation.
In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and histologically normal benign (HNB) tissues from patients were microdissected. RNA was isolated, amplified linearly, labeled, and hybridized to whole transcriptome microarrays to determine gene expression profiles. Genes that were differentially expressed between AH and HNB were identified using a paired analysis. Gene expression signatures distinguishing AH and HNB were defined using AGNES and PAM methods. Regulation of gene networks was investigated using breast epithelial cell lines, explant cultures of normal breast tissue and mouse tissues.
A 99-gene signature discriminated the histologically normal and AH tissues in 81% of the cases. Network analysis identified coordinated alterations in signaling through ERα, epidermal growth factor receptors, and androgen receptor which were associated with the development of both lobular and ductal AH. Decreased expression of SFRP1 was also consistently lower in AH. Knockdown of SFRP1 in 76N-Tert cells resulted altered expression of 13 genes similarly to that observed in AH. An SFRP1-regulated network was also observed in tissues from mice lacking Sfrp1. Re-expression of SFRP1 in MCF7 cells provided further support for the SFRP1-regulated network. Treatment of breast explant cultures with rSFRP1 dampened estrogen-induced progesterone receptor levels.
The alterations in gene expression were observed in both ductal and lobular AH suggesting shared underlying mechanisms predisposing to AH. Loss of SFRP1 expression is a significant regulator of AH transcriptional profiles driving previously unidentified changes affecting responses to estrogen and possibly other pathways. The gene signature and pathways provide insights into alterations contributing to AH breast lesions.
Background
Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein‐Barr virus–based markers is possible, the performance of diagnostic methods for detecting ...lesions among screen‐positive individuals is poorly understood.
Methods
The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population‐based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow‐up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated.
Results
Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; Pdifference = .021) and for early‐stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early‐stage disease and were more commonly observed for tumors originating from the pharyngeal recess.
Conclusions
MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen‐positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened.
This prospective study of people at high risk of nasopharyngeal carcinoma (NPC) shows that magnetic resonance imaging (MRI) screening is significantly more sensitive than endoscopy for detecting NPC and early‐stage NPC. There is also a higher overall rate of referral by MRI versus endoscopy, and this leads to a slightly lower positive predictive value for MRI versus endoscopy.
Cancer risk in living kidney donors Engels, Eric A.; Fraser, Gary E.; Kasiske, Bertram L. ...
American journal of transplantation,
August 2022, Letnik:
22, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and ...cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995–2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS‐2) participants, who typically have healthy lifestyles. During follow‐up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76–0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR < 1.00). Compared with AHS‐2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non‐Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54–2.79) and kidney cancer (2.97, 1.58–5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors’ remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.
This registry‐based study demonstrates that live kidney donors in the United States have an elevated risk of subsequent kidney cancer which, though small in absolute magnitude, may reflect adverse processes in the donors' remaining kidney. Sharif comment on (page 1941)
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