PTEN positive

These findings underscore the importance of PTEN in breast cancer biology and its potential as a therapeutic target. Furthermore these findings confirm the prevalence of advanced stage and aggressive breast cancer tumors in Ghana.

P1, N=18, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

This association is integral as it is the foremost site for PTEN to oppose PI3K/AKT pathway and consequently upregulate autophagy. Thus, this study indicates that sumoylation and phosphorylation of PTEN can control autophagy via its cell membrane association.

There were 2 MSI-H subtypes、1 high copy-number subtype、 68 low copy-number subtypes and no POLE mutations. Univariate and multivariate logistic analysis showed those PTEN-positive、ER and PR high-expression were more likely to achieve 3-month CR (OR=24.811、P=0.034; OR=9.428、 P=0.025; OR=29.178、P=0.011). Univariate and multivariate COX regression analysis showed that patients with high-expression PIK3CA were more likely to recurrence (OR=12.750、P=0.017).

Daily oral administration of edelfosine in murine prostate restricted AKT kinase transgenic mice, expressing active AKT in a prostate-specific manner, and in a DU145 xenograft mouse model resulted in significant tumor regression and apoptosis in tumor cells. Taken together, these results show a significant in vitro and in vivo antitumor activity of edelfosine against prostate cancer, and highlight the endoplasmic reticulum as a novel and promising therapeutic target in prostate cancer.

Although a distinct cutoff by which CNV differentiated PTEN-positive tumors from those with PTEN loss was not identified, higher copy number of PTEN may confer positive PTEN, whereas lower copy number of PTEN would necessitate additional testing by IHC to assess PTEN loss. NCT02276443.

Therefore, PTEN deficiency and high phosphorylation of DCK predict a better response to gemcitabine-based chemotherapy in CCA. We speculate that the combination of PP2A inhibitor and gemcitabine in PTEN-positive tumors could avoid the resistance of gemcitabine, which would benefit a large population of patients with cancer receiving gemcitabine or other nucleoside analogs.

P1, N=18, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=28 --> 18

P1, N=28, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

The findings suggest that PARG overexpression is a promising immunohistochemical marker to predict the occurrence and prognosis of EC. Moreover, PARG inhibition produced antitumor effects and increased the sensitivity of EC cells with PTEN deficiency to cisplatin.

Despite evident cell-type specificity in both maximally-synergistic combinations and the pathways that phytochemicals modulate, these combinations interact with similar prostate cancer protein targets. Here, we identify an approach that, when coupled with advanced data analysis methods, may suggest optimal dietary phytochemical combinations for individual consumption based on tumour molecular profile.Graphical abstract.

Mutation status was associated with improvements in PFS in FL pts with mutant BCL2 or mutant EZH2 treated with C+R. iNHL pts with low plasma levels of IL2 levels treated with C+R showed a significant improvement in OS.

Malignant tumours were found to have a statistically significant higher allele frequency (AF). The aggressive nodules were all poorly differentiated thyroid carcinomas (PDTCs) with copy number alterations (CNAs) and the highest AFs.

Proteomic analysis demonstrated a relative paucity of tumor-infiltrating lymphocytes in PTEN(-) versus adjacent PTEN(+) areas. The findings add to the understanding of potential molecular intratumoral heterogeneity in melanoma and the features associated with loss of PTEN protein in this disease.

A significant increase in the DNA breaks and the extent of apoptosis, possibly due to the failure of DNA repair, was observed upon PARP1 knockdown in the MDA-MB-468 cells compared with the case in the MDA-MB-231 cells. Our findings suggest that the synthetic lethal approach via PARP1 gene silencing holds promise for the treatment of patients with PTEN-null breast cancer.

Our results indicate that the relationship between BMI-1 and phosphatases involved in AKT regulation depends on the glucose concentration and insulin stimulation.

P1, N=28, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2020 --> Dec 2022 | Trial primary completion date: Dec 2020 --> Dec 2022

The analysis of pS133CREB and pS157VASP allows measuring activation of PKA signaling downstream of beta-2 adrenoreceptors. Presented results on the ratio of propranolol/epinephrine and the time needed to inhibit signaling downstream of beta-2 adrenoreceptors will help to design clinical studies that examine the effects of propranolol on prostate tumors.

KLK4::KLKP1 expression is more common in this cohort of Middle Eastern men than has been reported in North American men. It is associated with ERG positivity and inversely correlated with PTEN loss. In isolation, KLK4::KLKP1 expression was not significantly associated with clinical outcome or pathological parameters. However, its expression is associated with certain molecular subtypes (ERG-positive, PTEN-intact) and as we demonstrate may help further stratify the risk of recurrence within these groups.

Neuroendocrine tumours of the digestive tract have a distinct molecular profle that is still troublesome to understand regardless of grade, localization as well as other clinicopathological factors. We propose using PTEN expression as a signifcant negative prognostic factor for patients with NET of the digestive tract based on tumour grade and localization, but larger studies on more patients from each group are required in order to introduce PTEN expression in the treatment protocols.

Additionally, deguelin displayed a significant antitumor ability by upregulating PTEN and KLF4 expressions in mice model with NSCLC cells. Together, these results indicated that deguelin could be a potential therapeutic agent through upregulating PTEN and KLF4 expressions for NSCLC therapy.

C + R improved median PFS in the overall iNHL, FL, and non-FL groups, with a statistically significant improvement in the PTEN-positive population. In the P + R group, PTEN-positive patients had worse PFS in all 3 subgroups. Data from GEP and pathway analysis did not show correlation with overall response or PFS.

PTEN expression is significantly associated with ER/PR/AR status and loss of PTEN predicts poor PFS in HGSCs. TIL densities and PD-L1 expression are not affected by PTEN status. CCNE1 amplification, proposed as a marker for platinum resistance, is mutually exclusive with PTEN loss.

As a proof of concept, we have demonstrated that Dasatinib, a Src/Abl inhibitor approved for B-cell Acute Lymphoblastic Leukemia and Chronic Myelogenous Leukemia, is highly effective in PTEN-positive DLBCLs, irrespective of their COO class (Scuoppo et al., PNAS 2019)...First, we found that the activities of three chemically distinct drugs (FK-866, STF-118804 and KPT-9274) were highly correlated across the 34 lines DLBCL panel...These results were validated in xenotransplants of luciferized DLBCL lines and Patient Derived Xenotransplant models (PDXs) that were transcriptionally classified for the status of the Kynurenine De Novo signature. Together, these data support the repositioning of NAMPT inhibitors as a therapeutically relevant strategy for EZB-type GCB-DLBCLs.

Accordingly, elimination of TSPYL5 by inhibiting TSPYL5-pT120 can block aberrant AKT/TSPYL5/PTEN cyclic signaling and TSPYL5-mediated cancer stemness regulation. Our study suggests TSPYL5 be an effective target for therapy-resistant cancer.

PTEN negative indicated a shorter PFS and worse prognosis than PTEN positive in NPC patients. K and K derived from DCE-MRI, which yielded reliable capability, may be considered as potential imaging markers that are correlated with PTEN expression and could be used to predict PTEN expression noninvasively. Combined radiological and clinical features can improve the performance of the classification of PTEN expression.

Positive PTEN protein expression correlates with less myometrial invasion.

These data suggest a mechanism by which high glucose activates neddylation. PTEN is critical, if not indispensable, for MLN4924 suppression of tumor growth; PTEN status thus may help to identify MLN4924-responsive breast cancer patients.

An increase in stromal desmoplasia modifies differentiation, invasive and proliferative capacity of tumour cells. As phosphatase and tensin homologue functions through P-Akt pathway, P-Akt with phosphatase and tensin homologue could be a therapeutic target.

PTEN knockdown did not affect the cytostatic effect of 5-FU and cisplatin, whereas Tmab combined with the PI3K/mTOR inhibitor NPV-BEZ235 suppressed PTEN-knockdown cell proliferation. In patients with HER2-GEA, PTEN loss is a predictive biomarker of Tmab resistance and prognostic factor. Molecular-targeted therapy with a PI3K/mTOR inhibitor would be effective for HER2-GEA with PTEN loss.

Nearly half of mCRC cases (46.8%, aCRCS A1+B1) respond well to IRI, while only about 18.5% (aCRCS B2) of mCRC cases respond well to OX. In conclusion, the aCRCS might be a predictive factor of the clinical outcomes of OX- and IRI-based therapies.

Phosphatase and tensin homolog deleted on chromosome10 (PTEN), phospho-v-Akt murine thymoma viral oncogene homolog (AKT), and the Rapamycin-Insensitive Companion of mTOR (Rictor) expression was investigated by immunohistochemistry in 10 canine mammary adenomas (CMAs), 40 canine mammary carcinomas (CMCs), and 30 feline mammary carcinomas (FMCs)...PTEN expression was inversely correlated with p-AKT and Rictor in both species, while p-AKT positively correlated with Rictor expression. A strong PTEN/AKT pathway involvement in behavior worsening of CMT and FMTs is demonstrated, providing a rationale for further studies of this pathway in veterinary oncology.