Cancer treatment and research communications最新文献

Background

Targeting the costimulatory receptor CD137 has shown promise as a therapeutic approach for cancer immunotherapy, resulting in anti-tumor efficacy demonstrated in clinical trials. However, the initial CD137 agonistic antibodies, urelumab and utomilumab, faced challenges in clinical trials due to the liver toxicity or lack of efficacy, respectively. Concurrently, c-MET has been identified as a highly expressed tumor-associated antigen (TAA) in various solid and soft tumors.

Methods

In this study, we aimed to develop a bispecific antibody (BsAb) that targets both c-MET and CD137, optimizing the BsAb format and CD137 binder for efficient delivery of the CD137 agonist to the tumor microenvironment (TME). We employed a monovalent c-MET motif and a trimeric CD137 Variable Heavy domain of Heavy chain (VHH) for the BsAb design.

Results

Our results demonstrate that the c-MET x CD137 BsAb provides co-stimulation to T cells through cross-linking by c-MET-expressing tumor cells. Functional immune assays confirmed the enhanced efficacy and potency of the c-MET x CD137 BsAb, as indicated by activation of CD137 signaling, target cell killing, and cytokine release in various tumor cell lines. Furthermore, the combination of c-MET x CD137 BsAb with Pembrolizumab showed a dose-dependent enhancement of target-induced T cell cytokine release.

Conclusion

Overall, the c-MET x CD137 BsAb exhibits a promising developability profile as a tumor-targeted immune agonist by minimizing off-target effects while effectively delivering immune agonism. It has the potential to overcome resistance to anti-PD-(L)1 therapies.

Introduction

Previous studies have identified an interaction between protein kinase inhibitors (PKIs) and proton pump inhibitors (PPIs) in patients with lung cancer. This type of interaction may reduce the efficacy of PKIs. However, the effect of PKI-PPI interaction on patient mortality remains controversial. This study set out to determine the impact of PKI-PPI interaction on overall survival for lung cancer patients.

Materials and methods

This study was conducted using data from the French National Health Care Database from January 1, 2011 to December 31, 2021. We identified patients with: (i) an age equal to or greater than 18 years; (ii) lung cancer; and (iii) at least one reimbursement for one of the following drugs: erlotinib, gefitinib, afatinib and osimertinib. Patients were followed-up between the first date of PKI reimbursement and either December 31, 2021 or if they died, the date on which death occurred. The cumulative exposure to PPI duration during PKI treatment was calculated as the ratio between the number of concomitant exposure days to PKI and PPI and the number of exposure days to PKI. A survival analysis using a Cox proportional hazards model was then performed to assess the risk of death following exposure to a PKI-PPI interaction.

Results

34,048 patients received at least one reimbursement for PKIs of interest in our study: 26,133 (76.8 %) were exposed to erlotinib; 3,142 (9.2 %) to gefitinib; 1,417 (4.2 %) to afatinib; and 3,356 (9.9 %) to osimertinib. Patients with concomitant exposure to PKI-PPI interaction during 20 % or more of the PKI treatment period demonstrated an increased risk of death (HR, 1.60 [95 % CI, 1.57–1.64]) compared to other patients. When this cut-off varied from 10 % to 80 %, the estimated HR ranged from 1.46 [95 % CI, 1.43–1.50] to 2.19 [95 % CI, 2.12–2.25].

Discussion/Conclusion

In our study, an elevated risk of death was observed in patients exposed to PKI-PPI interaction. Finally, we were able to identify a dose-dependent effect for this interaction. This deleterious effect of osimertinib and PPI was revealed for the first time in real life conditions.

Introduction

Testing for mutations of epidermal growth factor receptor (EGFR) is crucial to identify non-small cell lung cancer (NSCLC) patients eligible for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs); This study aims to describe EGFR-mutation testing, treatment patterns, and overall survival (OS) in localized NSCLC patients.

Materials and Methods

Patients with localized (Stage IB–IIIA) NSCLC registered in the Norwegian Cancer Registry during 2010–2017 were followed from diagnosis until emigration, death, or end of study in 2018. The cohort was linked to data from the Norwegian Patient Registry, the Prescription Database, and the Cause of Death Registry.

Results

Of 2367 patients identified with localized NSCLC, 52 % were females and median age at diagnosis was 69 years. Most (66 %) were treated with surgery, while 16 % received curatively-intended radiotherapy (RT). EGFR-mutation testing increased significantly from 58 to 84 % during the study period. Testing frequencies varied across regions and comorbidity levels. Nine-percent of tested patients were EGFR-mutation positive (EGFRm+), of whom 27 % were treated with EGFR-TKIs. There was no correlation between initial treatment with either surgery or RT and EGFR-TKI use. The 3-year OS did not vary considerably by EGFR-mutation testing, but EGFRm+ patients had a higher 3-year OS (78.8 %) than wild-type EGFR (EGFRwt) patients (65.9 %).

Discussion

Although EGFR-mutation testing is increasingly being implemented in the early-stage setting in line with national recommendations, some patients are still not being tested for molecular markers as part of their diagnostic workup–a prerequisite for providing equal access to effective targeted treatments, such as EGFR-TKIs, to eligible patients.

Functional materials are required to meet the needs of society, such as environmental protection, energy storage and conversion, integrated product production, biological and medical processing. bulk nanostructured materials are a research concept that combines nanotechnology with other research fields such as supramolecular chemistry, materials science, and life science to develop logically functional materials from nanodevices. In this review article, nanostructures are synthetized by different methods based on the types and nature of the nanomaterials. In a broad sense “top-down” and “bottom-up” are the two foremost methods to synthesize nanomaterials. In top-down method bulk materials have been reduced to nanomaterials, and in case of bottom-up method, the nanomaterials are synthesized from elementary level. The different methods which are being used to synthesize nanomaterials are chemical vapor deposition method, thermal decomposition, hydrothermal synthesis, solvothermal method, pulsed laser ablation, templating method, combustion method, microwave synthesis, gas phase method, and conventional Sol-Gel method. We also briefly discuss the various physical and chemical methods for producing nanomaterials. We then discuss the applications of functional materials in many areas such as energy storage, supercapacitors, sensors, wastewater treatment, and other biological applications such as drug delivery and drug nanocrystals. Finally, future challenges in materials nanoarchitecture and concepts for further development of functional nanomaterials are briefly discussed.

Compared with the early symptoms of non-pregnancy, the early pregnancy with cervical cancer is often confused with threatened abortion, so it is difficult to diagnose and delay the time of treatment. At present, compared with cervical cancer, there is no clear and standard treatment for cervical cancer in pregnancy. At present, the diagnosis and treatment plan is mainly made according to the pathological examination, staging, fetal development (whether there is abnormality on ultrasound and whether the chromosome karyotype is normal or not) and the pregnant women and their family members’ pregnancy wishes. A case of pregnancy complicated with cervical cancer who was terminated by planned cesarean section after neoadjuvant chemotherapy (NACT) with irregular vaginal bleeding as the first symptom was analyzed retrospectively.

Purpose

Hodgkin's lymphoma is currently treated with a chemotherapy protocol consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine. Due to Brazil facing a bleomycin shortage in 2017, and this drug's high toxicity, this retrospective study evaluates the effect that the absence of bleomycin had on treatment response and overall survival of Hodgkin's lymphoma patients.

Methods

The medical records of 126 HL patients treated between 2007 and 2021 were reviewed and their data collected, followed by grouping into ABVD and AVD groups according to bleomycin use. Data concerning the patient's characteristics, cancer type, and treatment plan were analyzed with proportion tests, Kaplan-Meier curves. univariate Cox regression, and χ² tests.

Results

No discernible differences were found in this study between the overall survival and recurrence rate of patients treated with bleomycin compared to those without. Additionally, there was an increased risk of death in each subsequent cycle of chemotherapy of the complete ABVD protocol, demonstrating a risk of toxicity. Among the variables analyzed, hypertension and the presence of B symptoms were also associated with an increased risk of death, while the use of radiotherapy significantly improved survival.

Conclusion

The results of this study suggest that bleomycin did not impact the outcome of Hodgkin's lymphoma treatment. Moreover, the increased risk of death associated with its toxicity during each cycle of treatment raises concerns about its role as an essential component of the gold standard for Hodgkin's lymphoma treatment. Therefore, further research and consideration are needed to reassess the use of bleomycin in Hodgkin's lymphoma treatment protocols.

The multifactorial etiology underlying melanoma development involves an array of genetic, phenotypic, and environmental factors. Genetic predisposition for melanoma is further influenced by the complex interplay between high-, medium-, and low-penetrance genes, each contributing to varying degrees of susceptibility. Within this network, high-penetrance genes, including CDKN2A, CDK4, BAP1, and POT1, are linked to a pronounced risk for disease, whereas medium- and low-penetrance genes, such as MC1R, MITF, and others, contribute only moderately to melanoma risk. Notably, these genetic factors not only heighten the risk of melanoma but may also increase susceptibility towards internal malignancies, such as pancreatic cancer, renal cell cancer, or neural tumors. Genetic testing and counseling hold paramount importance in the clinical context of suspected hereditary melanoma, facilitating risk assessment, personalized surveillance strategies, and informed decision-making. As our understanding of the genomic landscape deepens, this review paper aims to comprehensively summarize the genetic underpinnings of hereditary melanoma, as well as current screening and management strategies for the disease.

Background

Rectal cancer (RC) poses a significant global health challenge, causing substantial morbidity and mortality. This study aims to investigate the survival rates of RC patients and identify the factors that influence their survival. The study considers demographic characteristics, tumor features, and treatment received as the factors under consideration.

Methods

A retrospective analysis was conducted on the medical records of 593 RC patients. Data were collected through a comprehensive review of medical records and conducting telephone interviews. Survival rates were estimated using the life table method, and subgroup comparisons were performed using the log-rank test. Cox regression analysis was utilized to assess the independent associations between RC survival time and various covariates.

Results

The study cohort comprised 593 RC patients, with a predominantly male representation. The mean age at diagnosis was 58.18 years, and the majority of patients (78.6 %) underwent surgical interventions. The median age at symptom onset and diagnosis were 58 and 59 years, respectively. Survival rates at 1st, 3rd, 5th, and 10th years were estimated to be 85 %, 59 %, 47 %, and 36 %, respectively. Statistical analysis revealed several significant prognostic factors, including age, education, symptoms, and cancer stage. In the multivariate Cox proportional-hazards analysis, advanced regional stage (HR = 1.54, 95 % CI, 1.13–2.08), presence of metastasis (HR = 3.73, 95 % CI, 2.49–5.58), and age over 70 (HR = 1.65) were associated with a higher risk of mortality.

Conclusion

Given the alarming prognosis of RC observed in the study area and the significant delay between symptom onset and diagnosis, it is crucial to address this issue and potentially improve the survival rates of RC patients.

Introduction

We have shown in a Phase I trial that immediate adjuvant chemotherapy (IAC) during surgical resection and immediately postoperative is safe and feasible in patients with colon cancer (CC). IAC avoids delays in adjuvant treatment and has the potential to improve survival and quality of life. We aim to determine patients and providers attitudes toward this novel multidisciplinary treatment approach.

Methods

Two web-based surveys were administered to newly diagnosed CC patients, survivors, surgeons and oncologists. Surveys assessed treatment preferences and perceived barriers to IAC. Chi-square tests were conducted to compare differences between patients’ and providers’ responses.

Results

Responses were collected from 35 patients and 40 providers. Patients were more willing to: (1) proceed with IAC to finish treatment earlier thus possibly improving quality of life (p = 0.001); (2) proceed with IAC despite potential side effects (p < 0.001); and (3) proceed with a dose of intraoperative chemotherapy even if on final pathology, may not have been needed (p = 0.002). Patients were more likely to indicate no barriers to collaborative care (p = 0.001) while providers were more likely to cite that it is time consuming, thus a barrier to participation (p = 0.001), has scheduling challenges (p = 0.001), and physicians are not available to participate (p = 0.003).

Conclusions

We observed a discordance between what providers and patients value in perioperative and adjuvant CC treatment. Patients are willing to accept IAC despite potential side effects and without survival benefit, highlighting the importance of understanding patient preference.

Tumors can produce bioactive substances called tumor-derived supernatants (TDS) that modify the immune response in the host body. This can result in immunosuppressive effects that promote the growth and spread of cancer. During tumorigenesis, the exudation of these substances can disrupt the function of immune sentinels in the host and reinforce the support for cancer cell growth. Tumor cells produce cytokines, growth factors, and proteins, which contribute to the progression of the tumor and the formation of premetastatic niches. By understanding how cancer cells influence the host immune system through the secretion of these factors, we can gain new insights into cancer diagnosis and therapy.