Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.

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Malignant Deciduoid Mesothelioma: A Diagnostic Challenge

Archives of Pathology & Laboratory Medicine ◽

10.5858/2005-129-403-mdmadc ◽

2005 ◽

Vol 129 (3) ◽

pp. 403-406 ◽

Cited By ~ 2

Author(s):

Najat Mourra ◽

Cecilede Chaisemartin ◽

Isabelle Goubin-Versini ◽

Rolland Parc ◽

Jean-Francois Flejou

Keyword(s):

Differential Diagnosis ◽

Cesarean Section ◽

Tumor Cells ◽

Elderly People ◽

Young Women ◽

Poor Prognosis ◽

Diagnostic Challenge ◽

Keratin 5 ◽

The Poor ◽

Rare Phenotype

Abstract Malignant deciduoid mesothelioma, a rare phenotype of epithelioid mesothelioma, arises more commonly from the peritoneum of young women, but it is also reported in the pleura of elderly people. We report a case of malignant deciduoid mesothelioma that occurred in a 41-year-old woman after cesarean section and was initially misdiagnosed as pseudotumoral deciduosis. Microscopically, the tumor was entirely composed of deciduoid areas, and only scattered tumor cells were positive for calretinin and keratin 5/6. The patient died 14 months after the first operation. This observation confirms the poor prognosis of this entity and the importance of the differential diagnosis of pseudotumoral deciduosis.

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Prognostic implications of caspase-3 expression in patients with diffuse large B-cell lymphoma (DLBCL)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17500 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17500-17500 ◽

Cited By ~ 1

Author(s):

W. H. Elsawy ◽

M. Abdel Kader ◽

A. Elfar ◽

A. Gharib ◽

S. Eltrhony ◽

...

Keyword(s):

B Cell ◽

Tumor Cells ◽

Poor Prognosis ◽

Caspase 3 ◽

Cell Lymphoma ◽

International Prognostic Index ◽

B Cell Lymphoma ◽

Serum Lactate Dehydrogenase ◽

Large B Cell Lymphoma ◽

Large B Cell

17500 Background: Caspase-3 activation is an essential step in programmed cell death (apoptosis) and cytotoxic drug-induced apoptosis is mediated by caspase-2 and caspase-3. The following study was designed to evaluate the correlation between Caspase-3 and the clinical outcome in patients with diffuse large B-cell lymphoma. Methods: Caspase-3 was determined by both immunohistochemistry and by quantitative reverse-transcription PCR in 49 previously untreated patients with diffuse large B-cell lymphoma. Results: Caspase-3 was positive in 69.4% of the patients by immunostaining and Tumor cells displayed a diffuse cytosolic expression in 51% of patients. The median value of Caspase-3mRNA within the group by quantitative PCR was 1. Caspase-3mRNA level was μ1 in 28 patients and <1 in 21 patients. Caspase-3 expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.02), and the International Prognostic Index (P = 0.0001). Patients with Caspase-3-positive immunostaining had a significantly higher complete response rate to chemotherapy and a longer overall survival than Caspase-3-negative patients. Also, patients with tumor cells expressing diffuse cytosolic immunostaining for caspase-3 had a poor prognosis when compared with those expressing a punctate staining (P > 0.0004 log-rank). A low caspase-3 mRNA expression by quantitative RT-PCR was also associated with a poor prognosis, although this was not statistically significant. In addition, patients with a high TUNEL positivity had a low survival probability (P > 0.02). Conclusions: Our results suggest that Caspase-3 activation or its lack may be a powerful independent predictor of response and survival in previously untreated diffuse large B-cell lymphomas. No significant financial relationships to disclose.

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Membranous CD44v6 is upregulated as an early event in colorectal cancer: Downregulation is associated with circulating tumor cells and poor prognosis

Oncology Letters ◽

10.3892/ol.2021.13081 ◽

2021 ◽

Vol 22 (6) ◽

Author(s):

Agapi Kataki ◽

Vassilis Giannakoulis ◽

Anastasia Derventzi ◽

Konstantinos Papiris ◽

Eythimios Koniaris ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Poor Prognosis ◽

Early Event

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Overexpression of the mitochondrial chaperone tumor necrosis factor receptor‑associated protein 1 is associated with the poor prognosis of patients with colorectal cancer

Oncology Letters ◽

10.3892/ol.2018.8042 ◽

2018 ◽

Author(s):

Chang Gao ◽

Min Li ◽

An‑Li Jiang ◽

Rui Sun ◽

Hong‑Lin Jin ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Necrosis Factor ◽

Poor Prognosis ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Receptor Associated Protein ◽

The Poor ◽

Necrosis Factor

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Circulating Tumor Cells in Right- and Left-Sided Colorectal Cancer

Cancers ◽

10.3390/cancers11081042 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1042 ◽

Cited By ~ 3

Author(s):

Chiara Nicolazzo ◽

Cristina Raimondi ◽

Angela Gradilone ◽

Alessandra Emiliani ◽

Ann Zeuner ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Poor Prognosis ◽

Median Number ◽

Tumor Location ◽

Prognostic Impact ◽

Primary Tumors ◽

Mesenchymal Phenotype

Molecular alterations are not randomly distributed in colorectal cancer (CRC), but rather clustered on the basis of primary tumor location underlying the importance of colorectal cancer sidedness. We aimed to investigate whether circulating tumor cells (CTC) characterization might help clarify how different the patterns of dissemination might be relative to the behavior of left- (LCC) compared to right-sided (RCC) cancers. We retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any first-line systemic treatment. Enumeration of CTC in left- and right-sided tumors were compared. The highest prognostic impact was exerted by CTC in left-sided primary cancer patients, even though the lowest median number of cells was detected in this subgroup of patients. CTC exhibit phenotypic heterogeneity, with a predominant mesenchymal phenotype found in CTC from distal compared to proximal primary tumors. Most CTC in RCC patients exhibited an apoptotic pattern. CTC in left-sided colon cancer patients exhibit a predominant mesenchymal phenotype. This might imply a substantial difference in the biology of proximal and distal cancers, associated with different patterns of tumor cells dissemination. The poor prognosis of right-sided CRC is not determined by the hematogenous dissemination of tumor cells, which appears to be predominantly a passive shedding of non-viable cells. Conversely, the subgroup of poor-prognosis left-sided CRC is reliably identified by the presence of mesenchymal CTC.

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Association of mesenchymal phenotype in circulating tumor cells with poor prognosis in metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14567 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14567-e14567

Author(s):

Arvind Dasari ◽

Hui Gao ◽

Laurel Deaton ◽

Michael J. Overman ◽

Siegfried Hauch ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Poor Prognosis ◽

Prognostic Significance ◽

Mesenchymal Transition ◽

Epithelial Markers ◽

Egfr Expression ◽

Aldh1 Expression

e14567 Background: Although the prognostic relevance of circulating tumor cells (CTCs) is well established in metastatic colorectal cancer (mCRC), their clinical use is currently constrained by the phenotypic definition of such cells that is largely limited to epithelial markers. Our objective in this study is to characterize the prognostic significance of a larger group of CTCs including those with characteristics of epithelial-mesenchymal transition (EMT) or cancer stem cells (CSCs) in a cohort of pre-treated mCRC patients (pts). Methods: Peripheral blood was collected in AdnaCollect preservation tubes from pts for immunomagnetic tumor cell enrichment using the AdnaTest ColonCancer Select kit and multiplex qRT-PCR analyses of tumor-associated epithelial (CEA, EPCAM, EGFR), cancer stem cell (ALDH1) and mesenchymal (TWIST1, AKT2, PIK3CA) transcripts. Results: In the initial phase, 41 previously treated mCRC pts (median prior therapies 3) were enrolled over a 4 month period and were followed prospectively. In this cohort, there was a low rate of CEA, EPCAM, and EGFR expression in the CTCs (12%, 2%, and 0%, respectively), consistent with loss of epithelial markers. Conversely, ALDH1, an established CSC marker was expressed in 30% of pts, with only one pt’s CTCs expressing both ALDH1 and CEA expression. ALDH1 expression was associated with very poor prognosis (HR 24.6, p=0.037) and 57% 60-day mortality, compared to 0% 60-day mortality for pts with no detectable ALDH1 expression. The mesenchymal markers of TWIST1, AKT2, and PIK3CA were strongly correlated with ALDH1 expression (Spearman r=0.55, 0.59, 0.63, respectively, p < 0.01 for each). Conclusions: The majority of CTCs detected in refractory mCRC pts have lost epithelial markers. Acquisition of markers associated with EMT or CSCs appear to be associated with poor prognosis, and may provide important insights into better prognostication and also biology of refractory colorectal cancer. Further enrolment into this study is ongoing and updated results will be presented.

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