CBMS-02 CROSSTALK WITH ASTROCYTES ESTABLISHES TUMOR EDGE IN GLIOBLASTOMA

Abstract Clinical outcomes for patients with glioblastoma (GBM) are extremely poor due to inevitable tumor recurrence even after extensive treatments. These recurrences are thought to manifest from cells located within the tumor edge. Despite this, the precise molecular mechanism governing GBM spatial phenotypic heterogeneity (e.g. edge vs. core) and subsequent tumor recurrence remains poorly elucidated. Here, using patient-derived GBM core and edge tissues, we analyzed transcriptional and metabolic signatures in an effort to determine how GBM facilitates the edge phenotype and its associated recurrence-initiating cells (RICs). In so doing, we unexpectedly identified CD38 as an essential protein in the formation of the edge phenotype and found a CD38-driven interaction between edge GBM cells and neighboring astrocytes that communally develops a GBM edge that is unresectable by surgery and retains RICs. These findings have profound implications for future clinical therapies and provide new mechanistic insights into both tumor progression and recurrence.

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Tumor control and trigeminal dysfunction improvement after stereotactic radiosurgery for trigeminal schwannomas: a systematic review and meta-analysis

Neurosurgical Review ◽

10.1007/s10143-020-01433-w ◽

2020 ◽

Author(s):

Iulia Peciu-Florianu ◽

Jean Régis ◽

Marc Levivier ◽

Michaela Dedeciusova ◽

Nicolas Reyns ◽

...

Keyword(s):

Trigeminal Neuralgia ◽

Tumor Progression ◽

Stereotactic Radiosurgery ◽

Clinical Outcomes ◽

Meta Analysis ◽

Symptomatic Improvement ◽

Tumor Control ◽

Linear Accelerators ◽

Oculomotor Nerves ◽

Clinical Worsening

AbstractTrigeminal nerve schwannomas (TS) are uncommon intracranial tumors, frequently presenting with debilitating trigeminal and/or oculomotor nerve dysfunction. While surgical resection has been described, its morbidity and mortality rates are non-negligible. Stereotactic radiosurgery (SRS) has emerged with variable results as a valuable alternative. Here, we aimed at reviewing the medical literature on TS treated with SRS so as to investigate rates of tumor control and symptomatic improvement. We reviewed manuscripts published between January 1990 and December 2019 on PubMed. Tumor control and symptomatic improvement rates were evaluated with separate meta-analyses. This meta-analysis included 18 studies comprising a total of 564 patients. Among them, only one reported the outcomes of linear accelerators (Linac), while the others of GK. Tumor control rates after SRS were 92.3% (range 90.1–94.5; p < 0.001), and tumor decrease rates were 62.7% (range 54.3–71, p < 0.001). Tumor progression rates were 9.4% (range 6.8–11.9, p < 0.001). Clinical improvement rates of trigeminal neuralgia were 63.5% (52.9–74.1, p < 0.001) and of oculomotor nerves were 48.2% (range 36–60.5, p < 0.001). Clinical worsening rate was 10.7% (range 7.6–13.8, p < 0.001). Stereotactic radiosurgery for TS is associated with high tumor control rates and favorable clinical outcomes, especially for trigeminal neuralgia and oculomotor nerves. However, patients should be correctly advised about the risk of tumor progression and potential clinical worsening. Future clinical studies should focus on standard reporting of clinical outcomes.

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Pan-Cancer Analysis Reveals that the SARS-CoV-2 Receptor ACE2 is a Protective Factor for Cancer Progression

10.21203/rs.3.rs-42534/v1 ◽

2020 ◽

Author(s):

Zhilan Zhang ◽

Lin Li ◽

Mengyuan Li ◽

Xiaosheng Wang

Keyword(s):

Tumor Progression ◽

Clinical Outcomes ◽

Cancer Progression ◽

Antitumor Immunity ◽

Protective Factor ◽

Cancer Genomics ◽

Mesenchymal Transition ◽

Expression Levels ◽

Oncogenic Pathways ◽

Pan Cancer

Abstract Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 13 million people and has caused more than 570,000 deaths worldwide as of July 13, 2020. The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection. Many studies have also explored the association between ACE2 and cancer. However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. Methods: Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between ACE2 expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 12 cancer cohorts. We also identified co-expression networks of ACE2 in cancer.Results: ACE2 upregulation was associated with increased antitumor immune signatures and PD-L1 expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. ACE2 expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-β, Wnt, VEGF, and Notch signaling pathways. Moreover, ACE2 expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition (EMT). ACE2 upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. Conclusions: ACE2 upregulation was associated with increased antitumor immunity and immunotherapy response, reduced tumor malignancy, and favorable survival in cancer, suggesting that ACE2 is a protective factor for cancer progression. Our data may provide potential clinical implications for treating cancer patients infected with SARS-CoV-2.

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Comparison of Surgical Outcomes and Recurrence Rates of Cystic and Solid Vestibular Schwannomas

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0039-1697039 ◽

2019 ◽

Author(s):

Rami O. Almefty ◽

David S. Xu ◽

Michael A. Mooney ◽

Andrew Montoure ◽

Komal Naeem ◽

...

Keyword(s):

Multivariate Analysis ◽

Facial Nerve ◽

Tumor Progression ◽

Clinical Outcomes ◽

Univariate Analysis ◽

Growth Patterns ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Tumor Diameter ◽

Cystic Tumors

Abstract Objective Cystic vestibular schwannomas (CVSs) are anecdotally believed to have worse clinical and tumor-control outcomes than solid vestibular schwannomas (SVSs); however, no data have been reported to support this belief. In this study, we characterize the clinical outcomes of patients with CVSs versus those with SVSs. Design This is a retrospective review of prospectively collected data. Setting This study is set at single high-volume neurosurgical institute. Participants We queried a database for details on all patients diagnosed with vestibular schwannomas between January 2009 and January 2014. Main Outcome Measures Records were retrospectively reviewed and analyzed using univariate and multivariate analyses to study the differences in clinical outcomes and tumor progression or recurrence. Results Of a total of 112 tumors, 24% (n = 27) were CVSs and 76% (n = 85) were SVSs. Univariate analysis identified the extent of resection, Koos grade, and tumor diameter as significant predictors of recurrence (p ≤ 0.005). However, tumor diameter was the only significant predictor of recurrence in the multivariate analysis (p = 0.007). Cystic change was not a predictor of recurrence in the univariate or multivariate analysis (p ≥ 0.40). Postoperative facial nerve and hearing outcomes were similar for both CVSs and SVSs (p ≥ 0.47). Conclusion Postoperative facial nerve outcome, hearing, tumor progression, and recurrence are similar for patients with CVSs and SVSs. As CVS growth patterns and responses to radiation are unpredictable, we favor microsurgical resection over radiosurgery as the initial treatment. Our data do not support the commonly held belief that cystic tumors behave more aggressively than solid tumors or are associated with increased postoperative facial nerve deficits.

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ADAM17 promotes the invasion of hepatocellular carcinoma via upregulation MMP21

Cancer Cell International ◽

10.1186/s12935-020-01556-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yuqi Xiang ◽

Liyu Liu ◽

Ying Wang ◽

Bo Li ◽

Jinwu Peng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Matrix Metalloproteinase ◽

Gene Family ◽

Tumor Progression ◽

Molecular Mechanism ◽

Cell Invasion ◽

Expression Level ◽

Invasion And Metastasis ◽

Direct Association ◽

The Relationship

Abstract Background The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21. Methods In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to confirmed that ADAM17 participated in the maturation of MMP21. Results Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17. Conclusion Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

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Distinct TP63 Isoform-Driven Transcriptional Signatures Predict Tumor Progression and Clinical Outcomes

Cancer Research ◽

10.1158/0008-5472.can-17-1803 ◽

2017 ◽

Vol 78 (2) ◽

pp. 451-462 ◽

Cited By ~ 12

Author(s):

Hussein A. Abbas ◽

Ngoc Hoang Bao Bui ◽

Kimal Rajapakshe ◽

Justin Wong ◽

Preethi Gunaratne ◽

...

Keyword(s):

Tumor Progression ◽

Clinical Outcomes

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1H-NMR-Based Metabolic Signatures of Clinical Outcomes in Trauma Patients—Beyond Lactate and Base Deficit

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0b013e3181e043fe ◽

2010 ◽

Vol 69 (1) ◽

pp. 31-40 ◽

Cited By ~ 38

Author(s):

Mitchell J. Cohen ◽

Natalie J. Serkova ◽

Jeanine Wiener-Kronish ◽

Jean-Francois Pittet ◽

Claus U. Niemann

Keyword(s):

Clinical Outcomes ◽

1H Nmr ◽

Base Deficit ◽

Trauma Patients ◽

Metabolic Signatures

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Effect of overexpression of human kinesin-14 family motor HSET on tumor progression and clinical outcomes in breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.1080 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 1080-1080

Author(s):

Vaishali Pannu ◽

Padmashree C.G. Rida ◽

Michelle D. Reid ◽

Oi Wah S. Yap ◽

Guilherme Henrique Cantuaria ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Progression ◽

Cancer Patients ◽

Clinical Outcomes ◽

Breast Cancer Patients

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DIFFERENTIAL DIAGNOSTICS OF A RADIONECROSIS AND LOCAL TUMORAL RECURRENCE ACCORDING TO ARTERIAL SPIN LABELLING AFTER RADIOSURGERY TREATMENT OF MALIGNANT GLIOMAS OF A BRAIN

Wiadomości Lekarskie ◽

10.36740/wlek202010110 ◽

2020 ◽

Vol 73 (10) ◽

pp. 2160-2164

Author(s):

Andrey B. Gryazov ◽

Yulia V. Medvedovska ◽

Andrey A. Gryazov

Keyword(s):

Tumor Progression ◽

Surgical Resection ◽

Tumor Recurrence ◽

Stereotactic Biopsy ◽

Malignant Gliomas ◽

Arterial Spin Labelling ◽

Differential Diagnostics ◽

Local Tumor ◽

Local Tumor Recurrence ◽

Spin Labelling

The aim: Assessment of a possibility of performing differential diagnostics of the post-beam radio necrosis (PBRN) and the local recurrence (LR) after the carried-out stereotaxic radio surgery (SRS) according to perfusion on the basis of non-contrast pulse arterial backs markings (PASL). Materials and methods: In our research, we consider results of the stereotactic radiosurgery (SRS) which is carried out to 20 patients with the diagnosis the malignant glioma of a brain (MGB) in respect differential diagnostics of a local tumor recurrence and radionecrosis according to perfusion non-contrast MRT of a research on the basis of the sequence of PASL. The diagnosis of MGB before carrying out SRS was established to all 20 patients on the basis of a histologic research on data of a biopsy. From them the anaplastic astrocytoma (AnASTs, grade III) and at 14 – a glioblastoma was diagnosed for 6 patients (GBM, grade IV). Confirmations of the post-beam diagnosis it was carried out on the basis of a histologic research on results of a stereotactic biopsy or a surgical resection. Traditional methods of medical statistics were applied to processing of the statistical information obtained in a research at all its stages (calculation of average and relative sizes with their errors), also graphic and tabular methods were applied to rational evident statement of the received results. Results: The diagnosis of a local tumor recurrence according to a relative regional blood-groove on the basis of PASL was exposed to 8 patients and confirmed histologically (to 5 patients underwent surgical resection, 3 – according to biopsy data). Patients with a confirmed diagnosis of relapse according to biopsy were performed in 1 case, repeated radiosurgery and in 2 cases (with a diagnosis of multifocal continued growth of glioblastoma) – irradiation of the entire brain. Radionecrosis was diagnosed in 12 cases. In 6 cases, it was confirmed on the basis of clinical diagnostic data of dynamic observation of patients, in 3 cases – according to surgical resection, and in 3 cases – according to stereotactic biopsy. According to our data, the average rrCBF based on arterial spin labelling (PASL) rTPmean ≤ 0.8ml / 100g / minute most likely testified in favor of radionecrosis, average ≥ 1.5ml / 100g / min – in favor of tumor progression, the maximum rTPmax ≤ 1.3ml / 100g / min most likely testified in favor of radio-necrosis, the maximum indicator rTPmax≥ 1.8ml / 100g / min – in favor of tumor progression. Conclusions: According to a relative regional blood flow of rrCBF based on non-contrast PASL perfusion, it is possible to reliably carry out a differential diagnosis of radionecrosis and local tumor recurrence in patients undergoing radiosurgical treatment for malignant gliomas of the brain.

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Local tumor progression treated with Gamma Knife radiosurgery: differences between patients with 2–4 versus 5–10 brain metastases based on an update of a multi-institutional prospective observational study (JLGK0901)

Journal of Neurosurgery ◽

10.3171/2019.1.jns183085 ◽

2020 ◽

Vol 132 (5) ◽

pp. 1480-1489 ◽

Cited By ~ 4

Author(s):

Toru Serizawa ◽

Masaaki Yamamoto ◽

Yoshinori Higuchi ◽

Yasunori Sato ◽

Takashi Shuto ◽

...

Keyword(s):

Tumor Progression ◽

Gamma Knife ◽

Tumor Recurrence ◽

Prospective Observational Study ◽

Radiation Necrosis ◽

Gamma Knife Radiosurgery ◽

Maximum Diameter ◽

Local Tumor Progression ◽

Local Tumor ◽

Data Set

OBJECTIVEThe Japanese Leksell Gamma Knife (JLGK)0901 study proved the efficacy of Gamma Knife radiosurgery (GKRS) in patients with 5–10 brain metastases (BMs) as compared to those with 2–4, showing noninferiority in overall survival and other secondary endpoints. However, the difference in local tumor progression between patients with 2–4 and those with 5–10 BMs has not been sufficiently examined for this data set. Thus, the authors reappraised this issue, employing the updated JLGK0901 data set with detailed observation via enhanced MRI. They applied sophisticated statistical methods to analyze the data.METHODSThis was a prospective observational study of 1194 patients harboring 1–10 BMs treated with GKRS alone. Patients were categorized into groups A (single BM, 455 cases), B (2–4 BMs, 531 cases), and C (5–10 BMs, 208 cases). Local tumor progression was defined as a 20% increase in the maximum diameter of the enhanced lesion as compared to its smallest documented maximum diameter on enhanced MRI. The authors compared cumulative incidence differences determined by competing risk analysis and also conducted propensity score matching.RESULTSLocal tumor progression was observed in 212 patients (17.8% overall, groups A/B/C: 93/89/30 patients). Cumulative incidences of local tumor progression in groups A, B, and C were 15.2%, 10.6%, and 8.7% at 1 year after GKRS; 20.1%, 16.9%, and 13.5% at 3 years; and 21.4%, 17.4%, and not available at 5 years, respectively. There were no significant differences in local tumor progression between groups B and C. Local tumor progression was classified as tumor recurrence in 139 patients (groups A/B/C: 68/53/18 patients), radiation necrosis in 67 (24/31/12), and mixed/undetermined lesions in 6 (1/5/0). There were no significant differences in tumor recurrence or radiation necrosis between groups B and C. Multivariate analysis using the Fine-Gray proportional hazards model revealed age < 65 years, neurological symptoms, tumor volume ≥ 1 cm3, and prescription dose < 22 Gy to be significant poor prognostic factors for local tumor progression. In the subset of 558 case-matched patients (186 in each group), there were no significant differences between groups B and C in local tumor progression, nor in tumor recurrence or radiation necrosis.CONCLUSIONSLocal tumor progression incidences did not differ between groups B and C. This study proved that tumor progression after GKRS without whole-brain radiation therapy for patients with 5–10 BMs was satisfactorily treated with the doses prescribed according to the JLGK0901 study protocol and that results were not inferior to those in patients with a single or 2–4 BMs.Clinical trial registration no.: UMIN000001812 (umin.ac.jp)

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