SummaryBackgroundMost head and neck squamous-cell carcinomas (HNSCCs) are driven by p16 INK4A inactivation and cyclin D1 overexpression that results in hyperactivation of cyclin-dependent kinase 4 ...and 6 (CDK4/6), rather than by the human papillomavirus (HPV). Deregulated cyclin D1 expression also causes resistance to EGFR inhibitors. We previously reported that palbociclib (a selective CDK4/6 inhibitor) given with cetuximab (an EGFR inhibitor) was safe. The aim of this study was to establish the proportion of patients achieving an objective response with palbociclib and cetuximab in recurrent or metastatic HNSCC. MethodsWe did a multicentre, multigroup, phase 2 trial to evaluate the activity of palbociclib and cetuximab in platinum-resistant (group 1) and cetuximab-resistant (group 2) HPV-unrelated HNSCC. The study was done across eight university sites in the USA. Eligibility required measurable disease (according to Response Evaluation Criteria in Solid Tumors, version 1·1 RECIST 1·1), Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, age of 18 years or older, and disease progression on platinum but cetuximab-naive (group 1) or disease progression on cetuximab (group 2). All patients received palbociclib orally (125 mg/day, on days 1–21) and intravenous cetuximab (400 mg/m 2 on cycle one, day 1, then 250 mg/m 2 once per week) in 28-day cycles. The primary endpoint was objective response (complete responses and partial responses per RECIST 1·1). Analyses were done per protocol. This trial was registered with ClinicalTrials.gov, NCT02101034, and is ongoing, but both groups are closed to accrual. FindingsBetween Oct 19, 2015, and Nov 7, 2018, 62 patients were enrolled onto the trial: 30 patients were enrolled in group 1 and 32 in group 2. Median follow-up was 5·4 months (IQR 4·4–12·1) for group 1 and 5·5 months (4·3–8·3) for group 2. In group 1, of 28 evaluable patients, an objective response was achieved by 11 (39%; 95% CI 22–59). In group 2, of 27 evaluable patients, an objective response was achieved by five (19%; 6–38) in group 2. The most common grade 3–4 palbociclib-related adverse event was neutropenia (in 21 34% of 62 patients). No treatment-related deaths occurred. InterpretationIn patients with platinum-resistant or cetuximab-resistant HPV-unrelated HNSCC, palbociclib and cetuximab results in promising activity outcomes. Further studies of CDK4/6 inhibitors are warranted in HPV-unrelated HNSCC. FundingPfizer.
Mono‐ to few‐layers of 2D semiconducting materials have uniquely inherent optical, electronic, and magnetic properties that make them ideal for probing fundamental scientific phenomena up to the 2D ...quantum limit and exploring their emerging technological applications. This Review focuses on the fundamental optoelectronic studies and potential applications of in‐plane isotropic/anisotropic 2D semiconducting heterostructures. Strong light–matter interaction, reduced dimensionality, and dielectric screening in mono‐ to few‐layers of 2D semiconducting materials result in strong many‐body interactions, leading to the formation of robust quasiparticles such as excitons, trions, and biexcitons. An in‐plane isotropic nature leads to the quasi‐2D particles, whereas, an anisotropic nature leads to quasi‐1D particles. Hence, in‐plane isotropic/anisotropic 2D heterostructures lead to the formation of quasi‐1D/2D particle systems allowing for the manipulation of high binding energy quasi‐1D particle populations for use in a wide variety of applications. This Review emphasizes an exciting 1D–2D particles dynamic in such heterostructures and their potential for high‐performance photoemitters and exciton–polariton lasers. Moreover, their scopes are also broadened in thermoelectricity, piezoelectricity, photostriction, energy storage, hydrogen evolution reactions, and chemical sensor fields. The unique in‐plane isotropic/anisotropic 2D heterostructures may open the possibility of engineering smart devices in the nanodomain with complex opto‐electromechanical functions.
This Review presents recent research progress toward in‐plane isotropic/anisotropic 2D van der Waals semiconducting heterostructures, a unique 1D/2D quasiparticle dynamics in these types of heterostructures, and their potential future applications in nanoelectronics and optoelectronics. This Review also highlights intriguing prospects of these types of 2D heterostructure in thermoelectricity, piezoelectricity, photostriction, energy storage, hydrogen evolution reactions, and chemical sensors.
2D materials based on main group element compounds have recently attracted significant attention because of their rich stoichiometric ratios and structure motifs. This review focuses on the phases in ...various 2D binary materials including III–VI, IV–VI, V–VI, III–V, IV–V, and V–V materials. Reducing 3D materials to 2D introduces confinement and surface effects as well as stabilizes unstable 3D phases in their 2D form. Their crystal structures, stability, preparation, and applications are summarized based on theoretical predictions and experimental explorations. Moreover, various properties of 2D materials, such as ferroelectric effect, anisotropic optical and electrical properties, ultralow thermal conductivity, and topological state are discussed. Finally, a few perspectives and an outlook are given to inspire readers toward exploring 2D materials with new phases and properties.
2D materials based on main group element compounds exhibit rich stoichiometries and structure motifs. The synthesis of these multiphase materials is controllable using new methodologies. Furthermore, their properties are revealed based on theoretical predictions and experimental exploration, and then developed for various potential applications.
Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of ...immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet.
A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included.
At the phylum level, patients who had enriched abundance in
and
almost universally had better response from ICIs, whereas those who were enriched in
universally presented with unfavorable outcome. Mixed correlations were observed for
in relating to treatment response. Regarding the AEs,
correlated to higher incidence whereas
were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of "ICI-favoring" gut microbiome (
= 0.0476).
Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.
Since the Ti3C2 was discovered in 2011, the family of MXenes has attracted much attention. MXenes offer great potential in the tuning of many fundamental properties by the synthesis of new ...structures. The synthesis methods of MXene mainly require steps including immersing a MAX phase in hydrofluoric acid (HF) and processing at high temperatures. However, the HF may be hard to acquire in many countries and processing at high temperatures may cause risk issues. In this article, a simple and cost‐effective synthesis of Ti3C2Tx quantum dots (QDs) via chemical solution method that follows the long‐time magnetic stirring process‐initiated etching of Al atoms from commercial Ti3AlC2 powder at room temperature is introduced. With WS2 monolayer sitting over the MXenes QD arrays, a higher level of photoluminescence (PL) enhancement is found in the heterostructure with increasing laser power at room temperature and a few novel quasi‐particles species in the heterostructure at −190 °C. The observations show that the possible plasmonic behavior initiated by QD arrays and the suspension state of WS2 may coplay the roles to trigger multiple quasi‐particles species. This study can be an important benchmark for the extensive understanding of quasi‐particles species, and their dynamics.
This article presents a simple and cost‐effective synthesis of Ti3C2Tx MXene quantum dots (QDs) via chemical solution method at room temperature. More specifically, with WS2 monolayer sitting over these MXene QD arrays, a higher level of photoluminescence (PL) enhancement with increasing laser power at room temperature, and a few of novel quasi‐particles species at −190 °C are introduced.
Adenoid cystic carcinoma (ACC) is a rare epithelial tumor of the salivary glands with an indolent course and usually bears a long-term survival rate even when metastasized. Spontaneous regression of ...such a resistant tumor is an even scarce event. We report a case of a patient with ACC of the parotid gland with pulmonary metastases, which spontaneously resolved following resection and post-surgical radiation of the primary tumor. Among the numerous theories proposed to explain such a phenomenon, immunogenic mechanisms and the abscopal effect are the most plausible explanations in this case.
Abstract
MXenes are a rapidly growing family of 2D materials. Their unique combination of metallic conductivity, hydrophilicity, and highly charged surfaces endow them with excellent electrochemical ...performance. Appropriate surface functional groups determine their semiconducting properties. The wide selection of various MXene structures and surface functional groups enable tunable work functions and bandgaps, making them prime candidates for many optoelectronic applications. In addition, the discovery of 2D organic semiconductors having single molecular thickness has also greatly attracted research attention due to their optical, electronic, optoelectronic, and mechatronic properties. Moreover, the formation of MXenes/organic 2D heterostructures enables many interesting phenomena in the 2D quantum limit to be observed. This review aims to increase motivation toward the investigation of newly emerging MXenes, 2D organic materials, and their combinational heterostructures. It overviews recent progress in the fundamental investigations of the optical, electronic, and optoelectronic properties in isolated 2D MXenes and organic materials; then, highlights the major importance of 2D MXene/organic heterostructures for applications in exciton–polariton lasers, light emitting devices, wearable electronics, and spintronic devices. The review aims outlines a future roadmap for 2D MXenes, organic materials, and their heterostructures for advanced nanotechnology applications.
Breast is an uncommon site of extra nodal lymphoma accounting for 2.2% of all extra nodal lymphomas. B cell lymphomas are more common than T cell types. The most common subtype is Diffuse Large B ...Cell Lymphoma. Breast lymphoma is very challenging to diagnose as it has nonspecific clinical and radiological features. We report a rare case of primary T cell lymphoma in a 20-year-old female. It was misdiagnosed as abscess on ultrasound and as suppurative mastitis on fine needle aspiration cytology (FNAC). However, excisional biopsy was suggestive of lymphoma and immunohistochemistry confirmed it as ALK positive, anaplastic large cell lymphoma. Even though FNAC is a part of the diagnostic triad for breast lesions, potential pitfalls cannot be overlooked and must be correlated with biopsy.
Two-dimensional materials (2Dm) offer a unique insight into the world of quantum mechanics including van der Waals (vdWs) interactions, exciton dynamics and various other nanoscale phenomena. 2Dm are ...a growing family consisting of graphene, hexagonal-Boron Nitride (h-BN), transition metal dichalcogenides (TMDs), monochalcogenides (MNs), black phosphorus (BP), MXenes and 2D organic crystals such as small molecules ( e.g. , pentacene, C8 BTBT, perylene derivatives, etc. ) and polymers ( e.g. , COF and MOF, etc. ). They exhibit unique mechanical, electrical, optical and optoelectronic properties that are highly enhanced as the surface to volume ratio increases, resulting from the transition of bulk to the few- to mono- layer limit. Such unique attributes include the manifestation of highly tuneable bandgap semiconductors, reduced dielectric screening, highly enhanced many body interactions, the ability to withstand high strains, ferromagnetism, piezoelectric and flexoelectric effects. Using 2Dm for mechanical resonators has become a promising field in nanoelectromechanical systems (NEMS) for applications involving sensors and condensed matter physics investigations. 2Dm NEMS resonators react with their environment, exhibit highly nonlinear behaviour from tension induced stiffening effects and couple different physics domains. The small size and high stiffness of these devices possess the potential of highly enhanced force sensitivities for measuring a wide variety of un-investigated physical forces. This review highlights current research in 2Dm NEMS resonators from fundamental physics and an applications standpoint, as well as presenting future possibilities using these devices.
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