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Twelve-Year-Old Lady using Serious Macular Neuroretinopathy: A new Multimodal Retinal Analysis.
A better understanding of the various interactions among immune cell subsets in the peritoneal microenvironment is necessary to develop efficacious therapies. This review will discuss various cell subsets in the ovarian tumor microenvironment, current immunotherapy modalities to target or augment these immune subsets, and treatment challenges.Glioma is the most common primary malignant brain tumor with a poor prognosis. Immune checkpoint inhibitors have been of great interest in investigation of glioma treatments. Here, we report single-cell transcriptomic analyses of two tumor areas from an oligodendroglioma taken from a patient who had multiple tumor recurrences, following several chemotherapies and radiation treatments. The patient subsequently received nivolumab and was considered have disease progression based on conventional diagnostic imaging after two cycles of treatment. He underwent a debulking surgical resection and pathological diagnosis was recurrent disease. During the surgery, tumor tissues were also collected from the enhancing and non-enhancing areas for a scRNAseq analysis to investigate the tumor microenvironment of these radiographically divergent areas. The scRNAseq analysis reveals a plethora of immune cells, suggesting that the increased mass observed on MRI may be partially a result of immune cell infiltration. The patient continued to receive immunotherapy after a short course of palliative radiation and remained free of disease progression for at least 12 months after the last surgery, suggesting a sustained response to immunotherapy. The scRNAseq analysis indicated that the radiological progression was in large part due to immune cell infiltrate and continued immunotherapy led to a positive clinical outcome in a patient who would have otherwise been admitted to hospice care with halting of immunotherapy. Our study demonstrates the potential of scRNAseq analyses in understanding the tumor microenvironment, which may assist the clinical decision-making process for challenging glioma cases following immunotherapy.Ovarian cancer is the deadliest gynecological cancer in women, with a survival rate of less than 30% when the cancer has spread throughout the peritoneal cavity. Aggregation of cancer cells increases their viability and metastatic potential; however, there are limited studies that correlate these functional changes to specific phenotypic alterations. In this study, we investigated changes in mitochondrial morphology and dynamics during malignant transition using our MOSE cell model for progressive serous ovarian cancer. Mitochondrial morphology was changed with increasing malignancy from a filamentous network to single, enlarged organelles due to an imbalance of mitochondrial dynamic proteins (fusion MFN1/OPA1, fission DRP1/FIS1). These phenotypic alterations aided the adaptation to hypoxia through the promotion of autophagy and were accompanied by changes in the mitochondrial ultrastructure, mitochondrial membrane potential, and the regulation of reactive oxygen species (ROS) levels. The tumor-initiating cells increased mitochondrial fragmentation after aggregation and exposure to hypoxia that correlated well with our previously observed reduced growth and respiration in spheroids, suggesting that these alterations promote viability in non-permissive conditions. Our identification of such mitochondrial phenotypic changes in malignancy provides a model in which to identify targets for interventions aimed at suppressing metastases.Radiation-induced late side effects such as cognitive decline and normal tissue complications can severely affect quality of life and outcome in long-term survivors of brain tumors. Proton therapy offers a favorable depth-dose deposition with the potential to spare tumor-surrounding normal tissue, thus potentially reducing such side effects. In this study, we describe a preclinical model to reveal underlying biological mechanisms caused by precise high-dose proton irradiation of a brain subvolume. We studied the dose- and time-dependent radiation response of mouse brain tissue, using a high-precision image-guided proton irradiation setup for small animals established at the University Proton Therapy Dresden (UPTD). The right hippocampal area of ten C57BL/6 and ten C3H/He mice was irradiated. Both strains contained four groups (nirradiated = 3, ncontrol = 1) treated with increasing doses (0 Gy, 45 Gy, 65 Gy or 85 Gy and 0 Gy, 40 Gy, 60 Gy or 80 Gy, respectively). Follow-up examinations were performed for up tort. The derived dose-response model will determine endpoint-specific dose levels for future experiments and may support generating clinical hypotheses on brain toxicity after proton therapy.The current research tested the hypothesis that inversion time (TI) shorter than 2,400 ms under 3T for FLAIR can improve the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas. We prepared three different cohorts; 94 MRI from 76 IDHmt, non-CODEL Lower-grade gliomas (LrGGs), 33 MRI from 31 LrGG under the restriction of FLAIR being acquired with TI less then 2,400 ms for 3T or 2,016 ms for 1.5T, and 112 MRI from 112 patients from the TCIA/TCGA dataset for LrGG. The presence or absence of the "T2-FLAIR mismatch sign" was evaluated, and we compared diagnostic accuracies according to TI used for FLAIR acquisition. The T2-FLAIR mismatch sign was more frequently positive when TI was shorter than 2,400 ms under 3T for FLAIR acquisition (p = 0.0009, Fisher's exact test). The T2-FLAIR mismatch sign was positive only for IDHmt, non-CODEL astrocytomas even if we confined the cohort with FLAIR acquired with shorter TI (p = 0.0001, Fisher's exact test). TCIA/TCGA dataset validated that the sensitivity, specificity, PPV, and NPV of the T2-FLAIR mismatch sign to identify IDHmt, non-CODEL astrocytomas improved from 31, 90, 79, and 51% to 67, 94, 92, and 74%, respectively and the area under the curve of ROC improved from 0.63 to 0.87 when FLAIR was acquired with shorter TI. We revealed that TI for FLAIR impacts the T2-FLAIR mismatch sign's diagnostic accuracy and that FLAIR scanned with TI less then 2,400 ms in 3T is necessary for LrGG imaging.
Tumor enucleation (TE) optimizes parenchymal preservation with promising short-term oncologic outcomes compared with standard partial nephrectomy (SPN). However, researches/literatures about long-term oncologic outcomes for TE after minimally invasive surgery are scarce. We aim to analyze long-term oncologic outcomes after laparoscopic and robotic tumor enucleation for renal cell carcinoma (RCC).

We retrospectively analyzed 146 patients who underwent TE with either laparoscopic or robotic approach for localized RCC in our center. Local recurrence, cancer specific survival (CSS), recurrence free survival (RFS), and overall survival (OS) were the main outcomes. Survival curves were generated using a Kaplan-Meier method. Perioperative outcomes and pathological outcomes were also analyzed.

Overall, 98 male and 48 female patients were eligible for the study. The median tumor size was 3.4cm with a median R.E.N.A.L. score of seven. Warm ischemia was used in 143 patients with a median ischemia time of 20min andin experienced hands for the treatment of RCC appears oncologically safe with a median follow-up of more than 5 years. Prospective studies with more patients and longer follow-up will be required to further evaluate oncologic safety after TE.
Epithelial mesenchymal transformation (EMT) and DNA repair status represent intrinsic features of colorectal cancer (CRC) and are associated with patient prognosis and treatment responsiveness. We sought to develop a combined EMT and DNA repair gene panel with potential application in patient classification and precise treatment.

We comprehensively evaluated the EMT and DNA repair patterns of 1,652 CRC patients from four datasets. Unsupervised clustering was used for classification. The clinical features, genetic mutation, tumor mutation load, and chemotherapy as well as immunotherapy sensitivity among different clusters were systematically compared. The least absolute shrinkage and selection operator regression method was used to develop the risk model.

Three distinct CRC clusters were determined. Clustet1 was characterized by down-regulated DNA repair pathways but active epithelial markers and metabolism pathway and had intermediate prognosis. Clustet2 was characterized by down-regulated both epithelial markers and DNA repair pathways and had poor outcome. Clustet3 presented with activation of DNA repair pathway and epithelial markers had favorable prognosis. Clustet1 might benefit form chemotherapy and Clustet3 had a higher response rate to immunotherapy. An EMT and DNA repair risk model related to prognosis and treatment response was developed.

This work developed and validated a combined EMT and DNA repair gene panel for CRC classification, which may be an effective tool for survival prediction and treatment guidance in CRC patients.
This work developed and validated a combined EMT and DNA repair gene panel for CRC classification, which may be an effective tool for survival prediction and treatment guidance in CRC patients.
Noninvasive evaluation of the expression of angiopoietin-2 (Ang-2) and transketolase (TKT) in hepatocellular carcinoma (HCC) is of great significance for the clinical development of individualized treatment plans. However, the correlation between intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and the expression of Ang-2 and TKT has not been reported. We sought to investigate the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.

Conventional non-enhanced magnetic resonance imaging (MRI) and IVIM-DWI and dynamic contrast MRI were performed for 61 patients with HCC before surgical treatment. Various IVIM-DWI parameters, such as apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D
) and fraction of fast apparent diffusion coefficient (f), were calculated using Function-MADC software. Expression levels of Ang-2 and TKT in HCC were detected
immunohistochemical staining and classified into two grades. Independent sample
tests were used to compare differences in parameters between the two groups. The Spearman rank correlation test was used to analyze the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.

The D
and f values were significantly higher in the high Ang-2 group than in the low Ang-2 group; there were no obvious between-group differences in ADC and D. Ang-2 expression was positively correlated with D* and f but not with ADC and D. The ADC and D values were significantly lower in the high TKT group than in the low TKT group, whereas the between-group differences for D* and f were not significant. TKT expression was negatively correlated with ADC and D but not with D* and f.

IVIM-DWI can be used to evaluate Ang-2 and TKT expression in HCC.
IVIM-DWI can be used to evaluate Ang-2 and TKT expression in HCC.Previous studies have revealed that TIPE1 serves as a tumor suppressor gene in several tumor types. However, we demonstrated that TIPE1 can promote cervical cancer proliferation by suppressing p53 activity. Here, we showed that TIPE1 inhibits cervical cancer cell apoptosis both in vivo and in vitro. Mechanistically, we revealed that TIPE1 facilitates chemoresistance in a wild-type p53-dependent manner. The results indicated that TIPE1 is responsible for the transition from chemosensitivity to chemoresistance, and that it can serve as a promising target in cervical cancer chemotherapy.
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