Change In Tumor Size Research Articles

A Case Report on the Therapeutic Effect of Integrated Cancer Therapy for Glioblastoma Multiforme

Objective: The purpose of this report is to present the effects of integrative cancer treatment (ICT) on a patient diagnosed with glioblastoma multiforme (GBM).Methods: A 71-year-old male GBM patient received ICT from May 14 to October 12, 2021 and concurrently received temozolomide and radiotherapy. The effect on symptoms was evaluated using a visual analog scale (VAS), and changes in tumor size were assessed using magnetic resonance imaging.Results: After treatment, the VAS score for nausea decreased from 5 to 1, and the tumor size also reduced.Conclusion: ICT could be effective in treating GBM patients by reducing the size of the tumor as well as alleviating the side effects.

Expression of Bax Protein as A Prognosis Factor of Radiotherapy Response to Decreased Tumor Size in Stage IIB-IIIB Cervical Cancer

Background: Cervical cancer plays a role as the leading cause of cancer death for women in developing countries. Radiation therapy kills cancer cells through double strand breaks and the apoptotic process. Bax protein is one of the regulators of apoptosis. This study analyzed the role of Bax expression as a prognostic factor in radiation therapy response in reducing tumor size in patients with advanced cervical cancer (IIB-IIIB). Subjects and Method: This research is a retrospective cohort observational analytic study from January 2021 to April 2021 in the Department of Obstetrics and Gynecology in collaboration with the Department of Anatomical Pathology, Dr. Moewardi Hospital, Surakarta, Indonesia. This study involved 30 cervical cancer stage IIB-IIIB patients. The level of Bax expression was determined by immunohistochemical examination. ROC curve analysis was used to find cut-off points and evaluate the sensitivity and specificity of Bax in the prognosis of radiotherapy in patients with advanced cervical cancer (IIB-IIIB). Chi square test was used to determine the relationship between Bax expression and changes in tumor size in cervical cancer patients. Results: The ROC curve analysis showed that the AUC Bax score in prognosis of radiation therapy was 0.575 (CI 95%= 0.32 to 0.83) and the cutoff point was 62.5%. Based on the analysis of the ROC curve, the Bax expression of 62.5% shows a sensitivity of 56.5% and a specificity of 71.4%. Analysis of the relationship between Bax protein expression on changes in tumor size using the Chi Square test showed a P value of 0.390 (p> 0.05). Conclusion: The expression of Bax protein cannot play a role as a prognostic factor in the response of radiation therapy to the reduction in tumor size in stage IIB-IIIB uterine cervical cancer.

Concordance of Clinician-Documented and Imaging Response in Patients With Stage IV Non–Small Cell Lung Cancer Treated With First-Line Therapy

In observational oncology studies of solid tumors, response to treatment can be evaluated based on electronic health record (EHR) documentation (clinician-assessed response [CAR]), an approach different from standardized radiologist-measured response (Response Evaluation Criteria in Solid Tumours [RECIST] 1.1). To evaluate the feasibility of an imaging response based on RECIST (IRb-RECIST) and the concordance between CAR and imaging response based on RECIST assessments, and investigate discordance causes. This cohort study used an EHR-derived, deidentified database that included patients with stage IV non-small cell lung cancer (NSCLC) diagnosed between January 1, 2011, to June 30, 2019, selected from 3 study sites. Data analysis was conducted in August, 2020. Undergoing first-line therapy and imaging assessments of response to treatment. In this study, CAR assessments (referred to in prior publications as "real-world response" [rwR]) were defined as clinician-documented changes in disease burden at radiologic evaluation time points; they were abstracted manually and assigned to response categories. The RECIST-based assessments accommodated routine practice patterns by using a modified version of RECIST 1.1 (IRb-RECIST), with independent radiology reads. Concordance was calculated as the percent agreement across all response categories and across a dichotomous stratification (response [complete or partial] vs no response), unconfirmed or confirmed. This study found that, in 100 patients evaluated for concordance, agreement between CAR and IRb-RECIST was 71% (95% CI, 61%-80%), and 74% (95% CI, 64%-82%) for confirmed and unconfirmed response, respectively. There were more responders using CAR than IRb-RECIST (40 vs 29 with confirmation; 64 vs 43 without confirmation). The main sources of discordance were the different use of thresholds for tumor size changes by RECIST vs routine care, and unavailable baseline or follow-up scans resulting in inconsistent anatomic coverage over time. In this cohort study of patients with stage IV NSCLC, we collected routine-care imaging, showing the feasibility of response evaluation using IRb-RECIST criteria with independent centralized review. Concordance between CAR and centralized IRb-RECIST was moderate. Future work is needed to evaluate the generalizability of these results to broader populations, and investigate concordance in other clinical settings.

A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies

Immunotherapy promotes the attack of cancer cells by the immune system; however, it is difficult to detect early responses before changes in tumor size occur. Here, we report the rational design of a fluorogenic peptide able to detect picomolar concentrations of active granzyme B as a biomarker of immune-mediated anticancer action. Through a series of chemical iterations and molecular dynamics simulations, we synthesize a library of FRET peptides and identify probe H5 with an optimal fit into granzyme B. We demonstrate that probe H5 enables the real-time detection of T cell-mediated anticancer activity in mouse tumors and in tumors from lung cancer patients. Furthermore, we show image-based phenotypic screens, which reveal that the AKT kinase inhibitor AZD5363 shows immune-mediated anticancer activity. The reactivity of probe H5 may enable the monitoring of early responses to anticancer treatments using tissue biopsies.

LncRNA PART1 inhibits glioma proliferation and migration via miR-374b/SALL1 axis

BackgroundAbnormal expression of lncRNA is involved in a diversity of diseases and plays a vital role in targeted therapy. However, few studies have been conducted on lncRNA PART1 in glioma. We aimed to investigate the function and the potential regulatory mechanism of lncRNA PART1/miR-374b/SALL1 axis in glioma. MethodsqRT-PCR and western blotting detected genes and proteins expression. Dual-luciferase reporter assay was performed to examine the binding relationship of lncRNA PART1, miR-374b, and SALL1. MTT assay and clone formation assay were performed to detect the cell viability and proliferation. Transwell assay detected glioma cell migration. In vivo tumor development experiments detected changes in tumor size, volume, and weight of the tumor after overexpression of lncRNA PART1. Immunohistochemistry was used to detect ki-67, E-cadherin, and N-cadherin expression. ResultsThe expression of lncRNA PART1 and SALL1 were down-regulated and miR-374b was up-regulated in different glioma cell lines. Overexpression of lncRNA PART1 inhibited glioma cell proliferation, migration, and epithelial mesenchymal transition (EMT). LncRNA PART1 targeted miR-374b to promote SALL1 expression. The knockdown of miR-374b inhibited glioma cell proliferation and migration and EMT by SALL1. What's more, overexpression of miR-374b or knockdown of SALL1 reversed the inhibitory effect of lncRNA PART1 on the proliferation, migration, and EMT of glioma cells. Furthermore, overexpression of lncRNA PART1 inhibited glioma growth in vivo. ConclusionLncRNA PART1 inhibited glioma proliferation and migration via miR-374b/SALL1 axis. These results might provide new insights for comprehending the complex lncRNA-miRNA network in gliomas.

Tumor Growth Inhibition-Overall Survival (TGI-OS) Model for Subgroup Analysis Based on Post-Randomization Factors: Application for Anti-drug Antibody (ADA) Subgroup Analysis of Atezolizumab in the IMpower150 Study.

Longitudinal changes of tumor size or tumor-associated biomarkers have been receiving growing attention as early markers of treatment benefits. Tumor growth inhibition-overall survival (TGI-OS) models represent mathematical frameworks used to establish a link from tumor size trajectory to survival outcome with the aim of predicting survival benefit with tumor data from a small number of subjects with a short follow-up time. In the present study, we applied the TGI-OS model to assess treatment benefit in the IMpower150 study for patients who exhibited development of anti-drug antibodies (ADA). Direct comparison between subgroups of the active arm [ADA positive (ADA +) and negative (ADA -) groups] to the entire control group is not appropriate, due to potential imbalances of baseline prognostic factors between ADA + and ADA - patients. Thus, the TGI-OS modeling framework was employed to adjust for differences in prognostic factors between the ADA subgroups to more accurately estimate the treatment benefits. After adjustment, the TGI-OS model predicted comparable hazard ratios (HRs) of OS between ADA + and ADA - subgroups, suggesting that the development of ADA does not have a clinically significant impact on the treatment benefit of atezolizumab.

Trans-arterial embolization of renal cell carcinoma: a systematic review and meta-analysis.

To evaluate if trans-arterial embolization (TAE) of the primary tumor in patients with renal cell carcinoma (RCC) improves symptomatology such as pain and hematuria or oncologic outcomes such as progression-free survival (PFS) and overall survival (OS). The systematic review search included PubMed, Ovid/MEDLINE, and Embase for full-text English articles including randomized and non-randomized prospective trials as well as prospective and retrospective case series. To be included, prospective trials needed ≥ 25 patients in each arm while case series and retrospective chart reviews required at least two patients. Evaluated outcomes included PFS, OS, change in tumor size, improvements in pain, improvements in hematuria, and adverse events (AEs). 1327 articles were retrieved and screened. Nine studies met inclusion criteria (retrospective case series, n = 8; non-randomized prospective trial, n = 1) which included 237 patients (M = 156 (65.8%); F = 56 (23.6%); gender unreported = 25 (10.5%); mean age: 69.4 (range: 38-87)) with a mean tumor diameter of 9.3cm (5.2-10.5). When reported, the TNM stages were stage I (n = 10), II (n = 18), III (n = 36), and IV (n = 121). 60 patients were treated for pain and hematuria. After TAE, pain improved in 59 patients (98.3%) and hematuria improved in 57 patients (95%). A meta-analysis for improvements in pain and hematuria demonstrated an event rate of pain improvement of 0.952 (0.788-0.990; p < 0.001) and an event rate for hematuria improvement of 0.923 (0.809-0.971; p < 0.001). Median OS ranged from 1 to 39months but only one study reported PFS (10.5months). Only one study demonstrated a statistically significant improvement in OS with TAE when compared with patients that did not undergo TAE (p = 0.02). A reduction in tumor size was only achieved in 17 patients (17/49; 34.7%) limiting evaluation. AEs included fever (n = 115/237; 48.5%), flank pain (n = 72/237; 30.4%), nausea (n = 58/237; 24.5%), hematuria (n = 12/237; 5.1%), hypertension (n = 12/237; 5.1%), reduced GFR (n = 6/237; 2.5%), hematoma (n = 6/237,2.5%), and ileus (n = 3/237; 1.3%). TAE monotherapy of the primary tumor in patients with RCC improves symptomatology such as pain and hematuria with an acceptable safety profile.

Are there country-specific differences in the use of pegvisomant for acromegaly in clinical practice? An analysis from ACROSTUDY

ObjectiveA comprehensive picture of pegvisomant use for treating acromegaly in routine clinical practice in different countries is lacking. We aimed, therefore, to document country-specific behaviors in real-life pegvisomant use, and the main safety and effectiveness outcomes in the ACROSTUDY.DesignACROSTUDY is an open-label, non-interventional, post-marketing safety surveillance study.MethodsA descriptive analysis was performed using data from the six top-recruiter ACROSTUDY countries, i.e., Germany (n = 548 patients), Italy (n = 466), France (n = 312), USA (n = 207), Spain (n = 200) and the Netherlands (n = 175). These nations accounted for > 85% of the ACROSTUDY cases.ResultsThe mean pegvisomant dose at treatment start was lowest in the Netherlands (9.4 mg/day), whereas it ranged between 10.9 and 12.6 mg/day in the other countries. At year 5, the mean pegvisomant dose was around 15 mg/day in all countries, except France (18.1 mg/day). At starting pegvisomant, patients treated with monotherapy ranged between 15% in the Netherlands and 72% in Spain. Monotherapy remained lowest over time in the Netherlands. In all countries, the percentage of patients with normal IGF-1 increased steeply from < 20% at baseline to 43–58% at month 6 and 51–67% at year 1. After that, we observed minor changes in the rate of acromegaly control in all countries. The Netherlands peaked in disease control at year 2 (72%). The proportion of patients reporting changes in pituitary tumor size was generally low. Serious treatment-related adverse events were < 5% in all countries.ConclusionsOur study provided a detailed summary of real-life use of pegvisomant in the six top-recruiter ACROSTUDY nations.

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study

BackgroundGenerally, a large tumor size of hepatocellular carcinoma (HCC) is associated with poor visibility and uncertainty in the surgical field which results in increased surgical difficulty as well as unfavorable postoperative outcomes. We performed intended preoperative trans-arterial embolization (TAE) in patients with a large HCC. In this study, we investigated the oncological significance of intended preoperative TAE for a large HCC, using a comparison between patients with and without TAE, and detailed analyses for pre- and post-TAE status.MethodsA total of 411 patients who underwent hepatectomy for primary HCC at the University of Yamanashi Hospital between January 2007 and December 2018 were included in this study. The patients were divided into two groups: patients with larger HCCs (≥50 mm, n=51) and those with smaller HCC (<50 mm, n=360) according to the size of their HCCs. Comparison of clinicopathological features between these groups and clinical outcomes between the TAE and non-TAE groups were compared. In addition, a detailed analysis of each case in the TAE group was conducted, comparing clinicopathological factors between pre- and post-TAE status.ResultsThe clinical unfavorable short- and long-term outcomes of patients with large HCCs (≥50 mm) were revealed compared to those with small HCCs (<50 mm). The prognostic analyses showed that a large tumor size and increased tumor markers, multiple tumor numbers, and others were adverse prognostic factors, and vascular invasions and residual tumors were included in the multivariate analysis.Further detailed analyses revealed that the average rates of change in tumor size and tumor shrinkage after TAE were − 48.6±35.6 mm and − 30.7±17.0%, respectively. Pathological high necrotic changes in the tumor, after multiple-times TAE aiming to a better effect, were related to a better prognosis in patients with large HCC. Poor prognostic factors became less common in patients who underwent intended preoperative TAE, and these patients had better prognoses.ConclusionsThe large tumor size of HCC is associated with unfavorable outcomes; the intended preoperative TAE for large HCC patients performed multiple times aiming to affect the tumor as much as possible might improve their prognoses.

Contrast-free MRI quantitative parameters for early prediction of pathological response to neoadjuvant chemotherapy in breast cancer.

To assess early changes in synthetic relaxometry after neoadjuvant chemotherapy (NAC) for breast cancer and establish a model with contrast-free quantitative parameters for early prediction of pathological response. From March 2019 to January 2021, breast MRI were performed for a primary cohort of women with breast cancer before (n = 102) and after the first (n = 93) and second (n = 90) cycle of NAC. Tumor size, synthetic relaxometry (T1/T2 relaxation time [T1/T2], proton density), and ADC were obtained, and the changes after treatment were calculated. Prediction models were established by multivariate logistic regression; evaluated with discrimination, calibration, and clinical application; and compared with Delong tests, net reclassification (NRI), and integrated discrimination index (IDI). External validation was performed from February to June 2021 with an independent cohort of 35 patients. In the primary cohort, all parameters changed after early treatment. Synthetic relaxometry decreased to a greater degree in major histologic responders (MHR, Miller-Payne G4-5) compared with non-MHR (Miller-Payne G1-3). A model combining ADC after treatment, changes in T1 and tumor size, and cancer subtype achieved the highest AUC after the first (primary/validation cohort, 0.83/0.82) and second cycles (primary/validation cohort, 0.85/0.84). No difference of AUC (p ≥ 0.27), NRI (p ≥ 0.31), and IDI (p ≥ 0.32) was found between models with different cycles and size-measured sequences. Model calibration and decision curves demonstrated a good fitness and clinical benefit, respectively. Early reduction in synthetic relaxometry indicated pathological response to NAC. Contrast-free T1 and ADC combined with size and cancer subtype predicted effectively pathological response after one NAC cycle. • Synthetic MRI relaxometry changed after early neoadjuvant chemotherapy, which demonstrated pathological response for mass-like breast cancers. • Contrast-free quantitative parameters including T1 relaxation time and apparent diffusion coefficient, combined with tumor size and cancer subtype, stratified major histologic responders. • A contrast-free model predicted an early pathological response after the first treatment cycle of neoadjuvant chemotherapy.

Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy.

BackgroundHost immune response is a critical component in tumorigenesis and immune escape. Radiation is widely used for glioblastoma (GBM) and can induce marked tissue inflammation and substantially alter host immune response. However, the role of myeloperoxidase (MPO), a key enzyme in inflammation and host immune response, in tumorigenesis after radiotherapy is unclear. In this study, we aimed to determine how post-radiation MPO activity influences GBM and outcome.MethodsWe injected C57BL/6J or MPO-knockout mice with 005 mouse GBM stem cells intracranially. To observe MPO's effects on post-radiation tumor progression, we then irradiated the head with 10 Gy unfractionated and treated the mice with a specific MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH), or vehicle as control. We performed semi-quantitative longitudinal molecular MRI, enzymatic assays and flow cytometry to assess changes in inflammatory response and tumor size, and tracked survival. We also performed cell culture experiments in murine and human GBM cells to determine the effect of MPO on these cells.ResultsBrain irradiation increased the number of monocytes/macrophages and neutrophils, and boosted MPO activity by ten-fold in the glioma microenvironment. However, MPO inhibition dampened radiation-induced inflammation, demonstrating decreased MPO-specific signal on molecular MRI and attenuated neutrophil and inflammatory monocyte/macrophage recruitment to the glioma. Compared to saline-treated mice, both ABAH-treated and MPO-knockout mice had accelerated tumor growth and reduced survival. We further confirmed that MPO decreased tumor cell viability and proliferation in cell cultures.ConclusionLocal radiation to the brain initiated an acute systemic inflammatory response with increased MPO-carrying cells both in the periphery and the GBM, resulting in increased MPO activity in the tumor microenvironment. Inhibition or absence of MPO activity increased tumor growth and decreased host survival, revealing that elevated MPO activity after radiation has an anti-tumor role.

Local tumour response to neoadjuvant therapy with 2-aminoethyl dihydrogen phosphate in dogs with soft tissue sarcoma.

BackgroundIn cases of soft tissue sarcoma (STS), neoadjuvant therapy is indicated to downstage the tumour prior to surgery to achieve enhanced local tumour control. The antineoplastic phospholipid compound 2‐aminoethyl dihydrogen phosphate (2‐AEH2F) is an alkyl phosphate ester capable of inhibiting cell proliferation and inducing cell death by modifying the asymmetry of phospholipids in the cytoplasmic membraneObjectivesThis clinical study was designed to investigate local antitumoural effects of neoadjuvant therapy with 2‐AEH2F in dogs with naturally occurring STSMaterial and methodsDogs (n = 11) received four consecutive weekly intravenous injections of 2‐AEH2F (70 mg/kg) prior to tumour resection. Tomographic (CT) and thermal (TE) images were used to investigate changes in tumour size and local temperature in response to treatmentResultsComparative analysis of CT images (n = 9/11) failed to reveal complete or partial remission according to selected assessment criteria (RECIST, WHO and volumetric). Comparative analysis of TE images (n = 10/11) revealed significantly (p = 0.01416) lower temperatures in tumoural areas relative to surrounding tissues over the course of treatmentConclusions2‐AEH2F had no cytoreductive effects when used at doses and intervals described in this study. However, significant drop in skin temperatures recorded in tumoural areas suggest induction of physiological changes.

A preliminary study of microwave ablation for solitary T1N0M0 papillary thyroid carcinoma with capsular invasion

Objective To evaluate the feasibility, efficiency, and safety of microwave ablation (MWA) for T1N0M0 papillary thyroid carcinoma (PTC) with capsular invasion (CI). Methods The data of 69 T1N0M0 PTC with CI underwent MWA from August 2015 to January 2020 were retrospectively analyzed. All PTC nodules were pathologically confirmed by fine needle aspiration (FNA). The extended ablation was performed in all cases, that is, the ablation zone completely covered the tumor and extended the tumor edge by at least 2 mm. The strategy of fluid isolation was successfully applied before and during ablation. The strategy of multiple point ablation was applied. After ablation, the changes in tumor size at different time points, local recurrence, new lesions, lymph node metastasis (LNM), and complications were evaluated and recorded. The technical feasibility, technical success rate, and safety were analyzed. Results Based on the contrast-enhanced ultrasound results, complete ablation has been achieved in all enrolled cases after ablation. The mean maximum tumor diameter and the mean volume of PTC nodules before ablation were 0.84 ± 0.39 cm (range, 0.3–2 cm) and 0.26 ± 0.35 ml (range, 0.01–1.72 ml) respectively. The mean follow-up time was 26 ± 10 months (range, 9–48 months). Nodules in 47 cases (68.1%) completely disappeared in the follow-up period. No local recurrence was detected. The incidence of new lesions and LNM was 4.3% (3/69) and 4.3% (3/69) respectively. Further ablations have been successfully employed for all of the new lesions and LMN. Light voice changes (2.9%, 2/69) were the only major complication, which was relieved within 6 months after MWA. The sizes of the ablation zone increased firstly within 6 months after MWA compared with the pretreatment tumor size (p < 0.05). Twelve months later, the sizes were smaller than those before MWA (p < 0.05 for all). Conclusions MWA is an effective, safe, and feasible method in treating T1N0M0 PTC with CI.

Optimizing pancreatic cancer management with next generation imaging and liquid biopsy (CHANGE-PDAC).

TPS640 Background: Pancreatic ductal adenocarcinoma (PDAC) is anticipated to become the second-leading cause of cancer-related deaths by 2030. Systemic therapy remains the mainstay of treatment for those with unresectable/metastatic disease. There is an urgent need for biomarkers to rapidly assess treatment response to spare patients from the significant toxicities and costs of an ineffective regimen, and to guide decision-making for a therapeutic switch with a higher chance of efficacy. Circulating tumor (ct)DNA and PET/MRI represent promising emerging biomarkers for early response prediction. This is a prospective non-randomized study examining the role of ctDNA and PET/MRI in adjudicating early treatment response among patients with unresectable locally advanced or metastatic PDAC receiving systemic therapy. Methods: Approximately 158 patients with advanced PDAC will be recruited at the time of initiation of a new line of treatment in either the first or later-line setting. Patients receiving both standard of care and/or experimental therapies are permitted to enroll. Research blood samples will be collected at pre-treatment, 48 hours, two weeks, one month, and two months after treatment start for analysis of mutant ctDNA (using the FoundationOne/Natera platform). PET/MRI will be performed at pre-treatment and 4 weeks post treatment. All patients must have an ECOG performance status of 0-2 and have radiographically measurable disease. Clinical data will be collected prospectively, including demographics, ECOG performance status, CA 19-9 levels, chemotherapy type and dose intensity, and clinical and radiographic assessment of treatment response using RECIST 1.1 criteria. Enrollment began in August 2021. The primary endpoint is the correlation between change in tumor-derived ctDNA with radiographic progression, as measured by the change in tumor size. The Wilcoxon rank sum test will be used to compare the change in ctDNA with treatment between response vs. resistance. Cox proportional hazard regression modelling will be used to correlate the change in ctDNA with progression-free survival and overall survival. Secondary endpoints include defining thresholds for early chemotherapy switch using dynamic and quantitative changes in ctDNA and PET/MRI biomarkers for use in future prospective trials, establishing the relationship between early changes in PET/MRI and treatment response/resistance, and developing a multivariable model combining ctDNA and PET/MRI biomarkers to predict treatment response/resistance.

DINs: Deep Interactive Networks for Neurofibroma Segmentation in Neurofibromatosis Type 1 on Whole-Body MRI.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that involves the central and peripheral nervous systems. Accurate detection and segmentation of neurofibromas are essential for assessing tumor burden and longitudinal tumor size changes. Automatic convolutional neural networks (CNNs) are sensitive and vulnerable as tumors' variable anatomical location and heterogeneous appearance on MRI. In this study, wepropose deep interactive networks (DINs) to address the above limitations. User interactions guide the model to recognize complicated tumors and quickly adapt to heterogeneous tumors. We introduce a simple but effective Exponential Distance Transform (ExpDT) that converts user interactions into guide maps regarded as the spatial and appearance prior. Comparing with popular Euclidean and geodesic distances, ExpDT is more robust to various image sizes, which reserves the distribution of interactive inputs. Furthermore, to enhance the tumor-related features, we design a deep interactive module to propagate the guides into deeper layers. We train and evaluate DINs on three MRI data sets from NF1 patients. The experiment results yield significant improvements of 44% and 14% in DSC comparing with automated and other interactive methods, respectively. We also experimentally demonstrate the efficiency of DINs in reducing user burden when comparing with conventional interactive methods.

Transplantation of feces from mice with Alzheimer's disease promoted lung cancer growth

BackgroundAlzheimer's disease (AD) is a progressive neurologic disorder that causes the brain to shrink and brain cells to die. Lung cancer is characterized by high morbidity and mortality, late diagnosis and poor prognosis. And there is no specific mechanism to explain the epidemiological correlation between AD and lung cancer. Materials and methodsLewis lung cancer cells (LLC) were injected into the left forelimb armpit of APP/PS1 mice to establish a tumor-bearing model. After remodeling the gut microbiota by fecal microbiota transplantation (FMT), the tumor were collected and analyzed for tumor size, Western blotting, and 16S rRNA gene sequencing. ResultsCompared with the control group, the AD FMT group showed larger tumors, while C57 FMT group showed smaller tumors. The former group showed the inhibition of AKT/Bax/Bcl-2 pathway, while the latter showed promotion of Caspase-1/IL-1β and AKT/Bax/Bcl-2 pathway, which induced changes in tumor size. And Prevotella, Prevotella, Mucispirillum and Halomonas in the gut lumen of LLC tumor-bearing mice are increased, and Bacteroides, Coprobacillus, Bifidobacterium, Faecalibacterium and Aggregatiacter are decreased significantly. ConclusionAD and lung cancer showed a positive correlation in APP expression, which proposed a different view from epidemiology on the correlation between AD and lung cancer.

FİBROİDLERİN DOPPLER ULTRASONOGRAFİ VE MANYETİK REZONANS GÖRÜNTÜLEMESİNİN KARŞILAŞTIRILMASI

OBJECTIVE: This study aimed to compare Doppler ultrasonography (USG) and magnetic resonance imaging (MRI) in the evaluation of various characteristics of myomas, including size and growth.MATERIAL AND METHODS: This descriptive study was conducted on female patients admitted to a private gynecology clinic in Turkey. Doppler USG and MRI measurements of the patients were performed and the following indices were calculated: Diastolic average ratio (DAR), Systolic/diastolic ratio (SDR), End-diastolic velocity (EDV), Peak systolic velocity (PSV), Acceleration time (AT), Time-averaged mean velocity (Tmean), Impedance index (LML), Acceleration index (AI), Diastolic/systolic ratio (DSR), Resistivity index (RI), Pulsatility index (PI), Time-averaged maximum velocity (TAMX). These indices were evaluated in the whole study group and also among those older than 49 years.RESULTS: Doppler USG and MRI results of PSV, EDV, TAMX, Tort, PI, RI, SDR, AT, AI, DSR, LML, DAR indexes and tumor size change averages were found to be similar in both the study group and women older than 49 years. It was found that there were strong positive correlations between Doppler USG and MRI measurements of PSV, EDV, TAMX, Tort, PI, RI, SDR, AT, AI, DSR, LML, DAR indices and tumor size change among the women in the study group.CONCLUSIONS: The results found in the research revealed that Doppler USG is as convenient as MRI in the diagnosis of myomas.

Treatment of Aggressive Retinal Astrocytic Hamartoma with Oral Mechanistic Target of Rapamycin Inhibition

To describe the clinical course and outcomes of aggressive retinal astrocytic hamartoma (RAH) treated with oral mechanistic target of rapamycin inhibitors (mTORis). A retrospective clinical case series. Five patients with genetically confirmed tuberous sclerosis complex and visually significant RAH due to tumor growth or exudation. In this retrospective clinical case series, a review of electronic medical records was performed to determine baseline and follow-up ophthalmic examination characteristics, along with ancillary imaging findings, in patients receiving off-label treatment with either oral sirolimus or everolimus for symptomatic RAH. Visual acuity, change in tumor size, degree of exudation, and adverse effects of the mTORis were evaluated. The 5 patients in this series ranged in age from 8 months to 54 years. Four were treated with sirolimus, and 1 received everolimus. In all the cases, the tumor height was stable or decreased after the treatment (median follow-up duration, 39 months; range, 11-73 months). Exudation improved after the treatment in all the cases. In an 8-month-old infant, frequent upper respiratory tract infections prompted the cessation of treatment. In 1 patient, the mTORi was temporarily withheld because of elevated liver enzyme levels. No other significant adverse effects were noted. Sirolimus and everolimus should be considered in the management of vision-threatening RAH, particularly in the setting of exudative and rapidly growing tumors. Four of the 5 patients in this series tolerated the oral mTORi and continued with the therapy. There were no serious complications.

Impact of CT-assessed changes in tumor size after neoadjuvant chemotherapy on pathological response and survival of patients with esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for advanced esophageal squamous cell carcinoma (ESCC) in Japan. Computed tomography (CT) is usually used to assess the therapeutic effect of NAC; however, there are no reliable criteria for predicting pathological response or patient prognosis. We included 84 patients who underwent esophagectomy between January 2009 and December 2018 and retrospectively reviewed their CT scans performed before and after NAC. The reduction rate of the largest tumor area (TA), long diameter (LD), and short diameter (SD) were measured on a transverse CT image. The pathological response and cutoff values were calculated using the receiver operating characteristic curve, and the most suitable ones for determining the effect were examined. The areas under the curve for predicting responders to NAC based on the reduction rate of the TA, LD, and SD were 0.755, 0.761, and 0.781, respectively. The optimal cutoff value of the SD reduction rate for predicting responders to NAC was 22%. An SD reduction ≥ 22% was an independent prognostic factor for overall survival in univariate (p = 0.005, hazard ratio [HR] = 2.755) and multivariate analyses (p = 0.030 HR 2.690). Furthermore, an SD reduction of ≥ 22% was also an independent prognostic factor for relapse-free survival in the univariate (p = 0.007, HR = 2.491) and multivariate analyses (p = 0.007, HR = 0.030). The reduction rate of the tumor SD is a simple predictor of pathological response and patient prognosis.

Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant.

Somatostatin exhibits an inhibitory effect on pituitary hormone secretion, including inhibition of growth hormone and adrenocorticotropic hormone (ACTH), and it can have antisecretory and antitumor effects on neuroendocrine tumors (NETs) that express somatostatin receptors. Although the precise mechanism remains unclear, the finding that glucocorticoids downregulate somatostatin receptor subtype 2 (SSTR2) expression has been used to explain the lack of efficacy of traditional SSTR2-targeting analogs in patients with ACTH-secreting NETs. Glucocorticoid receptor (GR) antagonism with mifepristone has been shown to reverse the glucocorticoid-induced downregulation of SSTR2; however, the effects of GR modulation on SSTR2 expression in ACTH-secreting NETs, particularly corticotroph pituitary tumors, are not well known. The current study presents new insight from in vitro data using the highly selective GR modulator relacorilant, showing that GR modulation can overcome dexamethasone-induced suppression of SSTR2 in the murine At-T20 cell line. Additional data presented from clinical case observations in patients with ACTH-secreting NETs suggest that upregulation of SSTR2 via GR modulation may re-sensitize tumors to endogenous somatostatin and/or somatostatin analogs. Clinical, laboratory, and imaging findings from 4 patients [2 ACTH-secreting bronchial tumors and 2 ACTH-secreting pituitary tumors (Cushing disease)] who were treated with relacorilant as part of two clinical studies (NCT02804750 and NCT02762981) are described. In the patients with ectopic ACTH secretion, SSTR2-based imaging (Octreoscan and 68Ga-DOTATATE positron emission tomography) performed before and after treatment with relacorilant showed increased radiotracer uptake by the tumor following treatment with relacorilant without change in tumor size at computed tomography. In the patients with Cushing disease who received relacorilant prior to scheduled pituitary surgery, magnetic resonance imaging after a 3-month course of relacorilant showed a reduction in tumor size. Based on these findings, we propose that GR modulation in patients with ACTH-secreting NETs upregulates previously suppressed SSTR2s, resulting in tumor-specific antisecretory and anti-proliferative effects. The effect of relacorilant on pituitary corticotroph tumors is being investigated in an ongoing phase 3 study (NCT03697109; EudraCT 2018-003096-35).