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1.
Adv Sci (Weinh) ; : e2404426, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976554

RESUMO

Waste plastics bring about increasingly serious environmental challenges, which can be partly addressed by their interconversion into valuable compounds. It is hypothesized that the porosity and acidity of a zeolite-based catalyst will affect the selectivity and effectiveness, enabling a controllable and selective conversion of polyethylene (PE) into gas-diesel or lubricating base oil. A series of embryonic, partial- and well-crystalline zeolites beta with adjustable porosity and acidity are prepared from mesoporous SBA-15. The catalysts and catalytic systems are studied with nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and adsorption kinetics and catalytic reactions. The adjustable porosity and acidity of zeolite-beta-based catalysts achieve a controllable selectivity toward gas-diesel or lubricating base oil for PE cracking. With a catalyst with mesopores and appropriate acid sites, a fast escape and reduced production of cracking of intermediates are observed, leading to a significant fraction (88.7%) of lubricating base oil. With more micropores, a high acid density, and strong acid strength, PE is multiply cracked into low carbon number hydrocarbons. The strong acid center of the zeolite is confirmed to facilitate significantly the activation of hydrogen (H2), and, an in situ ammonia poisoning strategy can significantly inhibit hydrogen transfer and effectively regulate the product distribution.

2.
J Appl Clin Med Phys ; : e14469, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031843

RESUMO

PURPOSE: To evaluate the dosimetric impact on spatially fractionated radiation therapy (SFRT) plan quality due to intrafraction patient motion via multi-field MLC-based method for treating large and bulky (≥8 cm) unresectable tumors. METHODS: For large tumors, a cone beam CT-guided 3D conformal MLC-based SFRT method was utilized with 15 Gy prescription. An MLC GTV-fitting algorithm provided 1 cm diameter apertures with a 2 cm center-to-center distance at the isocenter. This generated a highly heterogeneous sieve-like dose distribution within an hour, enabling same-day SFRT treatment. Fifteen previously treated SFRT patients were analyzed (5 head & neck [H&N], 5 chest and lungs, and 5 abdominal and pelvis masses). For each plan, intrafraction motion errors were simulated by incrementally shifting original isocenters of each field in different x-, y-, and z-directions from 1 to 5 mm. The dosimetric metrics analyzed were: peak-to-valley-dose-ratio (PVDR), percentage of GTV receiving 7.5 Gy, GTV mean dose, and maximum dose to organs-at-risk (OARs). RESULTS: For ±1, ±2, ±3, ±4, and ±5 mm isocenter shifts: PVDR dropped by 3.9%, 3.8%, 4.0%, 4.1%, and 5.5% on average respectively. The GTV(V7.5) remained within 0.2%, and the GTV mean dose remained within 3.3% on average, compared to the original plans. The average PVDR drop for 5 mm shifts was 4.2% for H&N cases, 10% for chest and lung, and 2.2% for abdominal and pelvis cases. OAR doses also increased. The maximum dose to the spinal cord increased by up to 17 cGy in H&N plans, mean lung dose (MLD) changed was small for chest/lung, but the bowel dose varied up to 100 cGy for abdominal and pelvis cases. CONCLUSION: Due to tumor size, location, and characteristics of MLC-based SFRT, isocenter shifts of up to ±5 mm in different directions had moderate effects on PVDR for H&N and pelvic tumors and a larger effect on chest tumors. The dosimetric impact on OAR doses depended on the treatment site. Site-specific patient masks, Vac-Lok bags, and proper immobilization devices similar to SBRT/SRT setups should be used to minimize these effects.

3.
Phys Med ; 123: 103408, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38889590

RESUMO

PURPOSE: This study aims to investigate lattice radiotherapy (LRT) for bulky tumor in 10 patients, analyzing geometrical and dosimetrical parameters and correlations among variables. METHODS: Patients were prescribed a single-fraction of 18 Gy to 50 % of each spherical vertex (1.5 cm diameter). Vertices were arranged in equidistant planes forming a triangular pattern. Center-to-center distance (Dc-c) between vertices was varied from 4 to 5 cm. A new method for calculating the valley-to-peak dose ratio (VPDR) was proposed and compared to other two from existing literature. GTV volumes (VGTV), vertex number (Nvert), low-dose related parameters and vertex D99%, D50%, and D1% were recorded. Beam-on time and Monitor Units (MU) were also evaluated. Correlations were assessed using Spearman's coefficient, with significant differences analyzed using Mann-Whitney U test. RESULTS: Tumor volumes ranged from 417 to 3615 cm3. Median vertex number was 14.5 (IQR:11.3-17.8). VPDR ranged from 0.16 to 0.28. Median D99% spanned from 10.0 to 13.7 Gy, median D50% exceeded 18.0 Gy, and median D1% surpassed 23.3 Gy. Periphery dose remained under 4.0 Gy. Plans exhibited high modulation, with median beam-on time and MU of 8.8 min (IQR:8.2-10.1) and 13,069 MU (IQR:11574-13639). Significant correlations were found between Nvert and VGTV (p < 0.01), MU (p < 0.02) and beam-on time (p < 0.01) and between Dc-c and two VPDR definitions (p < 0.02) and periphery dose (p < 0.01). Significant differences were observed among the three valley dose definitions (p < 0.01) and the three peak dose definitions (p < 0.01). CONCLUSIONS: Reporting geometrical and dosimetrical parameters in LRT is crucial, alongside the need for unified definitions of valley and peak doses.


Assuntos
Radiometria , Humanos , Dosagem Radioterapêutica , Neoplasias/radioterapia , Masculino , Planejamento da Radioterapia Assistida por Computador/métodos , Carga Tumoral , Feminino , Pessoa de Meia-Idade , Idoso , Fracionamento da Dose de Radiação
4.
Front Oncol ; 14: 1364627, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854732

RESUMO

Purpose: Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART. Methods and materials: We defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV's border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents. Results: 21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14-85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009). Conclusion: SCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

5.
Angew Chem Int Ed Engl ; 63(32): e202407503, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38781114

RESUMO

Sterically hindered pyridines embedded in a three-dimensional triptycene framework have been synthesized, and their resolution by chiral HPLC enabled access to unprecedented enantiopure pyridines exceeding the known steric limits. The design principles for new axially chiral pyridine derivatives are then described. To rationalize their associations with Lewis acids and transition metals, a comprehensive determination of the steric and electronic parameters for this new class of pyridines was performed. This led to the general parameterization of the steric parameters (percent buried volume %VBur, Tolman cone angle θ, and He8_steric descriptor) for a large set of two- and three-dimensional pyridine derivatives. These parameters are shown to describe quantitatively their interactions with carbon- and boron-centered Lewis acids and were used to predict the ΔG° of association with the prototypical B(C6F5)3 Lewis acid widely used in frustrated Lewis pair catalysis. This first parameterization of pyridine sterics is a fundamental basis for the future development of predictive reactivity models and for guiding new applications of bulky and chiral pyridines in organocatalysis, frustrated Lewis pairs, and transition-metal catalysis.

6.
Angew Chem Int Ed Engl ; 63(30): e202404264, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38699962

RESUMO

Using single-crystal to single-crystal solid/gas reactivity the gold(I) acetylene complex [Au(L1)(η2-HC≡CH)][BArF 4] is cleanly synthesized by addition of acetylene gas to single crystals of [Au(L1)(CO)][BArF 4] [L1=tris-2-(4,4'-di-tert-butylbiphenyl)phosphine, ArF=3,5-(CF3)2C6H3]. This simplest gold-alkyne complex has been characterized by single crystal X-ray diffraction, solution and solid-state NMR spectroscopy and periodic DFT. Bonding of HC≡CH with [Au(L1)]+ comprises both σ-donation and π-backdonation with additional dispersion interactions within the cavity-shaped phosphine.

7.
Chem Asian J ; 19(15): e202400498, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38760323

RESUMO

Reaction of lithium 1,3-diamidopropane Li2(TripNCN) (TripNCN=[{(Trip)NCH2}2CH2]2-, Trip=2,4,6-triisopropylphenyl) with BeBr2(OEt2)2 gave the diamido beryllium complex, [(TripNCN)Be(OEt2)]. Deprotonation reactions between the bulkier 1,3-diaminopropane (TCHPNCN)H2 (TCHPNCN=[{(TCHP)NCH2}2CH2]2-, TCHP=2,4,6-tricyclohexylphenyl) and magnesium alkyls afforded the adduct complexes [(TCHPNCN)Mg(OEt2)] and [(TCHPNCN)Mg(THF)2], depending on the reaction conditions employed. Treating [(TCHPNCN)Mg(THF)2] with the N-heterocyclic carbene :C{(MeNCMe)2} (TMC) gave [(TCHPNCN)Mg(TMC)2] via substitution of the THF ligands. Reactions of (ArNCN)H2 (Ar=Trip or TCHP) with Mg{CH2(SiMe3)}2, in the absence of Lewis bases, yielded the N-bridged dimers [{(ArNCN)Mg}2]. Salt metathesis reactions between alkali metal salts M2(TCHPNCN) (M=Li or K) and CaI2 or SrI2 led to the THF adduct compounds [(TCHPNCN)Ca(THF)3] and [(TCHPNCN)Sr(THF)4], the differing number of THF ligands in which is a result of the different sizes of the metals involved. The described complexes hold potential as precursors to kinetically protected, low oxidation state group 2 metal species.

8.
World J Clin Cases ; 12(10): 1851-1856, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38660077

RESUMO

BACKGROUND: Para-aortic lymph nodes (PALNs) are common sites for the regional spread of cervical squamous cell carcinoma (SCC). CASE SUMMARY: We report the case of a 36-year-old woman who presented with cervical SCC with multiple bulky PALNs, largest measured 4.5 cm × 5 cm × 10 cm. The patient was treated with radical intent with definitive chemoradiation using sequential dose-escalated adaptive radiotherapy, followed by maintenance chemotherapy. The patient achieved a complete response; she has been doing well since the completion of treatment with no evidence of the disease for 2 years. CONCLUSION: Regardless of the size of PALN metastases of cervical carcinoma origin, it is still treatable (with radical intent) via concurrent chemoradiation. Adaptive radiotherapy allows dose escalation with minimal toxicity.

10.
Cancer Res Treat ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605662

RESUMO

Purpose: This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. Materials and Methods: We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. Results: A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and 7 with bulky N+. The median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 stage, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. Conclusion: Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.

11.
Chemistry ; 30(30): e202400715, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38501797

RESUMO

The chemistry of extremely bulky amide ligands is troubled by difficulties in deprotonation of the parent amine. As an alternative route to superbulky amide reagents, the addition of polar reagents to a sila-imine has been investigated. Attempts to synthesize the superbulky amide anion (tBu3Si)2N- by addition of tBuLi to tBu2Si=N(SitBu3) failed and gave tBu3Si(tBu2HSi)NLi and isobutene. Reaction of the sila-imine with KOtBu successfully led to tBu3Si[tBu2(tBuO)Si]NK which crystallized as a separated ion-pair. Reaction with the slightly bulkier KOAd (Ad=1-adamantyl) led in presence of THF to ether ring-opening. Reaction with tBuOH gave tBu3Si[tBu2(tBuO)Si]NH but this amine cannot be easily deprotonated. Reaction with (BDI*)MgnBu in presence of THF gave (BDI*)Mg+ ⋅ (THF)2 and the non-coordinating anion tBu3Si[tBu2(nBu)Si]N-; BDI*=ß-diketiminate ligand HC[C(tBu)N-DIPP]2, DIPP=2,6-diisopropylphenyl. Reaction of Mg(nBu)2 with tBu2Si=N(SitBu3) led to a Mg complex with one amide ligand: tBu3Si[tBu2(nBu)Si]N-. The other superbulky amide anion isomerized by internal deprotonation of a tBu-substituent to give a primary carbanion that is also coordinated to Mg. Although the amide-to-carbanion isomerization is highly contrathermodynamic, it allows for coordination of both anions to a single Mg center. The new bulky amides are rare cases of halogen-free weakly coordinating anions.

12.
Hematol Oncol ; 42(2): e3261, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454623

RESUMO

To recognize patients at high risk of refractory disease, the identification of novel prognostic parameters improving stratification of newly diagnosed Hodgkin Lymphoma (HL) is still needed. This study investigates the potential value of metabolic and texture features, extracted from baseline 18F-FDG Positron Emission Tomography/Computed Tomography (PET) and Contrast-Enhanced Computed Tomography scan (CECT), together with clinical data, in predicting first-line therapy refractoriness (R) of classical HL (cHL) with mediastinal bulk involvement. We reviewed 69 cHL patients who underwent staging PET and CECT. Lesion segmentation and texture parameter extraction were performed using the freeware software LIFEx 6.3. The prognostic significance of clinical and imaging features was evaluated in relation to the development of refractory disease. Receiver operating characteristic curve, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate their prognostic value. Among clinical characteristics, only stage according to the German Hodgkin Group (GHSG) classification system significantly differed between R and not-R. Among CECT variables, only parameters derived from second order matrices (gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM) demonstrated significant prognostic power. Among PET variables, SUVmean, several variables derived from first (histograms, shape), and second order analyses (GLCM, GLRLM, NGLDM) exhibited significant predictive power. Such variables obtained accuracies greater than 70% at receiver operating characteristic analysis and their PFS curves resulted statistically significant in predicting refractoriness. At multivariate analysis, only HISTO_EntropyPET extracted from PET (HISTO_EntropyPET ) and GHSG stage resulted as significant independent predictors. Their combination identified 4 patient groups with significantly different PFS curves, with worst prognosis in patients with higher HISTO_EntropyPET values, regardless of the stage. Imaging radiomics may provide a reference for prognostic evaluation of patients with mediastinal bulky cHL. The best prognostic value in the prediction of R versus not-R disease was reached by combining HISTO_EntropyPET with GHSG stage.


Assuntos
Doença de Hodgkin , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos
13.
Eur J Surg Oncol ; 50(4): 108013, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401353

RESUMO

OBJECTIVE: We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. METHODS: We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). RESULTS: We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). CONCLUSION: No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments.


Assuntos
Metástase Linfática , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia , Feminino , Procedimentos Cirúrgicos de Citorredução , Taxa de Sobrevida , Intervalo Livre de Doença , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia
14.
Cureus ; 16(1): e51518, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38304655

RESUMO

Locally advanced prostate cancer may rarely present with bulky pelvic lymph nodes without distant metastasis. Patients may be treated with curative intent. Dual hormonal therapy including luteinizing hormone-releasing hormone agonist in combination with abiraterone or enzalutamide can be utilized neoadjuvantly to shrink bulky disease. This can be followed by radical doses of radiotherapy. This intensified treatment is tolerable. Prostate-specific membrane antigen scan can be utilized to assess staging and treatment response. Here, we present a case of a non-metastatic locally advanced prostate cancer with bulky pelvic lymph nodes. The patient was treated neoadjuvantly with dual hormonal therapy followed by radical doses of radiotherapy. The patient tolerated the treatment well and had a promising early response.

15.
J Gynecol Oncol ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38330380

RESUMO

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

16.
ACS Chem Neurosci ; 15(3): 608-616, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38241462

RESUMO

The introduction of arylmethyl substituents on the amine nitrogen atom of phenethylamines and tryptamines often results in profound increases in their affinity and functional activity at 5-HT2 serotonin receptors. To probe the sensitivity of this effect to substantially larger N-substituents, ten derivatives of the well-characterized psychedelic phenethylamine 2C-B were prepared by appending different dibenzo[b,d]furylmethyl (DBFM) moieties to the basic nitrogen. The DBFM group attached to the amino group through its 1-, -2-, or 3-position decreased affinity and agonist activity at the 5-HT2A/2C receptors. Substitution through the 4-position usually favored affinity for all three 5-HT2 receptor subtypes with compound 5 exhibiting 10- and 40-fold higher affinities at the 5-HT2A and 5-HT2C receptors, respectively, but less than fourfold selectivity among the three receptor subtypes. Nevertheless, all were relatively weak partial 5-HT2AR agonists, mostly in the low micromolar range, but full or nearly full agonists at the 5-HT2C subtype as determined in a calcium mobilization assay. Molecular docking simulations suggested that the dibenzofuryl portion dives more deeply into the orthosteric binding site of the 5-HT2A than the 5-HT2C receptor, interacting with the Trp3366.48 toggle switch associated with its activation, while the phenylamine moiety lies close to the extracellular side of the receptor. In conclusion, a very bulky N-substituent on a phenethylamine 5-HT2 receptor agonist is tolerated and may increase affinity if its orientation is appropriate. However, the Gq protein-mediated potencies are generally low, with low efficacy (relative to 5-HT) at the 5-HT2A receptor, somewhat higher efficacy at the 5-HT2B subtype, and full or nearly full efficacy at the 5-HT2C subtype.


Assuntos
Alucinógenos , Serotonina , Agonistas do Receptor 5-HT2 de Serotonina , Receptor 5-HT2A de Serotonina , Simulação de Acoplamento Molecular , Fenetilaminas , Nitrogênio , Receptor 5-HT2C de Serotonina
17.
Gastric Cancer ; 27(2): 366-374, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38180622

RESUMO

BACKGROUND: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.


Assuntos
Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/uso terapêutico , Gastrectomia/métodos , Metástase Linfática , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia
18.
Methods Mol Biol ; 2773: 97-104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38236540

RESUMO

Radiotherapy is a widely used approach for cancer treatment. However, delivering a single high dose of radiation to bulky tumors can be challenging due to the toxicities induced in the surrounding healthy tissue. To overcome this issue, a nonuniform high dose can be delivered using partial-volume tumor irradiation or spatially fractionated radiotherapy (SFRT). Moreover, SFRT has the potential to induce a stronger antitumor immune response compared to traditional radiotherapy due to the preservation of immune cells in the unirradiated tumor regions. There are several SFRT approaches, including GRID therapy, three-dimensional GRID therapy (LATTICE), microbeam radiation therapy (MRT), and Stereotactic Body Radiation Therapy for PArtial Tumor irradiation targeting exclusively the HYpoxic segment (SBRT-PATHY). The following protocol describes partial-volume tumor irradiation, a technique that enables dose delivery to only a part of the tumor in mice using an X-ray generator and collimators of different dimensions that limit the size of the irradiation field.


Assuntos
Fibras na Dieta , Neoplasias , Animais , Camundongos , Nível de Saúde , Hipóxia , Neoplasias/radioterapia
19.
Life (Basel) ; 13(12)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38137844

RESUMO

BACKGROUND: Gastric cancer is increasing worldwide and one million new cases were estimated globally in 2020. Use of the laparoscopic approach is increasing especially for subtotal gastrectomy. However, to date, solid data on locally advanced bulky tumors are lacking. The aim of this study is to assess the role of laparoscopic surgery in bulky gastric tumors. METHODS: We performed an observational retrospective single-center analysis. The following data were collected and analyzed for each patient: demographics, tumor-related data, intra-operative data, peri-operative data, and pathological data. Statistical analysis was conducted, including descriptive statistics and chi-squared test, to analyze the differences between categorical variables. RESULTS: O the 116 patients who underwent gastric surgery, 49 patients were included in the study protocol. All patients had bulky gastric tumors. Eighteen patients underwent laparoscopic gastrectomy and 31 open gastrectomy. The median number of lymph nodes removed was 28.5 (15-46) in the laparoscopic group and 23.05 (6-62) in the open group (p = 0.04). In total, 5.6% of patients of the laparoscopic group had <16 lymph nodes harvested and 35.5% in the open group (p = 0.035). No statistical differences were found between the open and laparoscopic groups in terms of surgical margins (p = 0.69). CONCLUSIONS: Laparoscopic surgery is still a subject of debate in locally advanced bulky gastric cancer. Limited data are available concerning Western patients. This study showed superiority in terms of the quality of lymphadenectomy and non-inferiority in terms of radical resection margins.

20.
Front Oncol ; 13: 1063438, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098510

RESUMO

Background: In early stage diffuse large B-cell lymphoma (ESDLBL), tumor bulkiness is an important determinant of treatment and prognosis. Tumor bulk is usually measured on transverse computed tomography (CT) plane and variably defined from 5 to 10 cm. Objectives: Our study aims to investigate the prognostic significance of bulky disease measured on CT coronal and transverse planes and to evaluate the outcome of patients with bulky disease. Methods: Patients with ESDLBL and treated with rituximab, cyclophosphamide, doxorubicin, and prednisolone (RCHOP) with or without radiotherapy were included. Receiver Operating Characteristic (ROC) analysis was used to identify the optimal tumor dimension that correlated with progression, relapse, or death. Correlation between different variables and progression-free survival (PFS) and overall survival (OS) were analyzed using log-rank (Mantel-Cox) test and Cox proportional hazard models. Results: A total of 127 patients with a median age of 47 (range: 18-90) years were included. Eighty-two (64.6%) patients treated with combined modality treatment (CMT) [RCHOP + radiotherapy]. After a median follow-up of 40 (range: 2-114) months, 3-year PFS and OS were 83.9% (95% CI: 76.759%-89.981%), and 80.6% (95% CI: 72.499%-87.531%), respectively. Tumor dimension of >7.5 cm measured on either CT plane was the optimal cutoff point to define bulky disease. Three-year PFS and OS were inferior in the group of patients with no bulky disease on transvers plane (n = 84) but had bulky disease on coronal plane (n = 9,10.7%); (94.2% vs. 75%, p = 0.017 and 90.5% vs. 56.3%, p = 0.002), as well as in patients with no bulky disease on coronal plane (n = 89), but had bulky disease on transverse plane (n = 14, 15.7%); (94.1% vs. 62.3%, p < 0.001, and 90.4% vs. 63.5%, p = 0.002). Compared to RCHOP alone, 3-year PFS and OS were better in patients with bulky disease treated with CMT (78% vs. 52.5%, p = 0.018 and 81.8% vs. 38.7%, p = 0.003) but not in patients with non-bulky disease (96.2% vs. 93%, p = 0.691 and 87.6% vs. 91.5%, p = 0.477). Conclusion: In ESDLBL, measurement of tumor mass on transverse and coronal CT planes may help in better identification of patients with bulky disease. The use of CMT was associated with better survival outcomes in patients with bulky disease.

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