Ki67 and P53 in Relation to Disease Progression in Metastatic Pancreatic Cancer: a Single Institution Analysis

Temraz, Sally; Shamseddine, Ali; Mukherji, Deborah; Charafeddine, Maya; Tfayli, Arafat; Assi, Hazem; Hammoud, Mohammad; Makki, Iman; Nassif, Samer

doi:10.1007/s12253-018-0464-y

Cited by 27 publications

(18 citation statements)

References 24 publications

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“…Several tissue markers have been proposed to have a prognostic impact on PC. As such, GATA6 expression allows a distinction between classical and basal-like subtypes [ 26 ]—with the latter being associated with chemoresistance and poor prognosis [ 27 , 28 , 29 ], while a high Ki-67 proliferation index is considered to have a negative impact on disease-free survival [ 30 , 31 , 32 ]. All available PDOs with the corresponding tumor tissue were evaluated for GATA6 and Ki-67 expression by immunohistochemistry ( Figure 4 A,D).…”

Section: Resultsmentioning

confidence: 99%

A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

Beutel

Schütte

Scheible

et al. 2021

Cancers

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Real-time isolation, propagation, and pharmacotyping of patient-derived pancreatic cancer organoids (PDOs) may enable treatment response prediction and personalization of pancreatic cancer (PC) therapy. In our methodology, PDOs are isolated from 54 patients with suspected or confirmed PC in the framework of a prospective feasibility trial. The drug response of single agents is determined by a viability assay. Areas under the curves (AUC) are clustered for each drug, and a prediction score is developed for combined regimens. Pharmacotyping profiles are obtained from 28 PDOs (efficacy 63.6%) after a median of 53 days (range 21–126 days). PDOs exhibit heterogeneous responses to the standard-of-care drugs, and are classified into high, intermediate, or low responder categories. Our developed prediction model allows a successful response prediction in treatment-naïve patients with an accuracy of 91.1% for first-line and 80.0% for second-line regimens, respectively. The power of prediction declines in pretreated patients (accuracy 40.0%), particularly with more than one prior line of chemotherapy. Progression-free survival (PFS) is significantly longer in previously treatment-naïve patients receiving a predicted tumor sensitive compared to a predicted tumor resistant regimen (mPFS 141 vs. 46 days; p = 0.0048). In conclusion, generation and pharmacotyping of PDOs is feasible in clinical routine and may provide substantial benefit.

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Section: Resultsmentioning

confidence: 99%

A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

Beutel

Schütte

Scheible

et al. 2021

Cancers

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“…As showed in Figure 7A and B, co-administration of FMT and CpG significantly suppressed the tumor growth in tumor-bearing mice. Ki-67, an antigen present in the nuclei of proliferating cells, is widely used to evaluate the proliferative activity of tumors 40. The immunohistochemical analysis revealed that the percentage of Ki-67- and EGFR-positive tumor cells in the FMT/CpG group was markedly lower than that in the control group (Figure 7D and E), whereas the percentage of M1 macrophages stained with F4/80 and iNOS in tumor tissues was significantly up-regulated (Figure 7F).…”

Section: Resultsmentioning

confidence: 99%

<p>Ferumoxytol and CpG oligodeoxynucleotide 2395 synergistically enhance antitumor activity of macrophages against NSCLC with EGFR<sup>L858R/T790M</sup> mutation</p>

Guo-qun¹,

Zhao²,

Zhang³

et al. 2019

IJN

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Purpose: Drug resistance is a major challenge for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) treatment of lung cancer. Ferumoxytol (FMT) drives macrophage (MΦ) transformation towards a M1-like phenotype and thereby inhibits tumor growth. CpG oligodeoxynucleotide 2395 (CpG), a toll-like receptor 9 (TLR9) agonist, is an effective therapeutic agent to induce anticancer immune responses. Herein, the effect of co-administered FMT and CpG on MΦ activation for treating non-small cell lung cancer (NSCLC) was explored. Methods: The mRNA expression levels of M1-like genes in RAW 264.7 MΦ cells stimulated by FMT, CpG and FMT and CpG (FMT/CpG) were evaluated by quantitative reverse transcription PCR (qRT-PCR). Then, the effects of FMT/CpG-pretreated MΦ supernatant on apoptosis and proliferation of H1975 cells were detected by flow cytometry, and the expression of EGFR and its downstream signaling pathway in H1975 cells were explored by western blotting. Finally, a H1975 cell xenograft mouse model was used to study the anti-tumor effect of the combination of FMT and CpG in vivo. Results: FMT and CpG synergistically enhanced M1-like gene expression in MΦ, including tumor necrosis factor-α, interleukin (IL)-12, IL-1α, IL-1β, IL-6 and inducible nitric oxide synthase (iNOS). FMT/CpG-pretreated MΦ supernatant inhibited proliferation and induced apoptosis of H1975 cells, accompanied by down-regulation of cell cycle-associated proteins and up-regulation of apoptosis-related proteins. Further studies indicated that the FMT/CpG-pretreated MΦ supernatant suppressed p-EGFR and its downstream AKT/mammalian target of rapamycin signaling pathway in H1975 cells. Furthermore, FMT/CpG suppressed tumor growth in mice accompanied by a decline in the EGFR-positive tumor cell fraction and increased M1 phenotype macrophage infiltration. Conclusion: FMT acted synergistically with CpG to activate MΦ for suppressed proliferation and promoted apoptosis of NSCLC cells via EGFR signaling. Thus, combining FMT and CpG is an effective strategy for the treatment of NSCLC with EGFR L858R/T790M mutation.

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“…The tumor also had a Ki67 index of 30%, with positive reactivity for P53, indicative of a relatively poor prognosis. [16]…”

Section: Discussionmentioning

confidence: 99%

An osteoclast-like giant cell tumor embedded in the mural nodule of a pancreatic mucinous cystic neoplasm

Fan

Wang

et al. 2019

Medicine

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Rationale: Mucinous cystic neoplasms (MCNs) are relatively rare lesions, accounting for 2%–5% of all exocrine pancreatic neoplasms. MCNs mainly occur in women (female:male ratio = 20:1), with a peak incidence in the 5th decade of life. Osteoclast-like giant cell tumors (OGCTs) are rare and relatively aggressive neoplasms, comprising <1% of all pancreatic carcinomas. Herein, we present a rare “combination tumor” case and discuss the impact of mural nodules in pancreatic MCNs considering malignant transformation. Patient concerns: A 54-year-old Mongolian man, without vomiting, nausea or jaundice, presented with abdominal distention since 3 months. He had a 7-year history of diabetes. Physical examinations indicated slight middle abdominal tenderness without rebound tenderness or rigidity. Laboratory results revealed that the level of carcinoembryonic antigen (CEA) was 1.16 ng/ml (normal: <5 ng/ml); CA-199: 30.02 U/ml (normal: <27 U/ml); hemoglobin: 143 g/L; fasting glucose: 7.71 mmol/L; and albumin: 43 g/L. Abdominal enhanced computed tomography revealed a 7 × 6 cm solid neoplasm in the pancreatic body with partial enhancement and heterogeneity. Endoscopic ultrasound revealed a solid-cystic space-occupying lesion in the pancreatic body. Diagnosis: The preoperative preliminary diagnosis was pancreatic solid-cystic tumor, possibly a solid pseudopapillary tumor. Postoperative pathological findings revealed a pancreatic borderline MCN with an OGCT embedded in a mural nodule of the capsule. Immunohistochemical results indicated a simultaneous dual origin from the epithelium and stroma. Interventions: The patient underwent open distal pancreatectomy and splenectomy. Postoperative blood glucose levels were closely monitored and regulated. We intravenously administered single-agent gemcitabine (1400 mg on day 1) as the first-time chemotherapy, 1 month after surgery. After the first chemotherapy, the patient refused to receive further treatment owing to personal reasons. Outcomes: The patient showed uneventful recovery and was discharged 13 days after the initial surgery. Follow-up was performed 1, 3 and 6 months after surgery. At 6 months, abdominal computed tomography scan showed no signs of recurrence, regional lymphadenopathy, or other abnormalities. And laboratory tests showed a platelet count of 301 × 10 9 /L, postprandial blood glucose of 12.9 mmol/L and CA-199 level of 20 U/ml. The patient had no obvious discomfort. Lessons: Although pancreatic MCNs are widely accepted as borderline tumors, malignant transformations may occur due to various risk factors (cyst size, mural nodules, septations, and tumor location). The combination tumor in this case was more likely to increase the possibility of malignant biological behavior, thereby worsening overall prognosis. Therefore, long-term follow-up must be maintained wit...

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Ki67 and P53 in Relation to Disease Progression in Metastatic Pancreatic Cancer: a Single Institution Analysis

Cited by 27 publications

References 24 publications

A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response

<p>Ferumoxytol and CpG oligodeoxynucleotide 2395 synergistically enhance antitumor activity of macrophages against NSCLC with EGFR<sup>L858R/T790M</sup> mutation</p>

An osteoclast-like giant cell tumor embedded in the mural nodule of a pancreatic mucinous cystic neoplasm

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