Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer: Evaluation of a biological-systems approach to cancer therapy (U.S. FDA IND-BB 10091; NCT 02046174, NCT 01053013)

Smith, Barry H.; Gazda, Lawrence S.; Fahey, Thomas J.; Nazarian, Angelica; Laramore, Melissa A.; Martis, Prithy C.; Andrada, Zoe P.; Thomas, Joanne; Parikh, Tapan; Sureshbabu, S.; Berman, Nathaniel; Ocean, Allyson J.; Hall, Richard D.; Wolf, David J.

doi:10.21147/j.issn.1000-9604.2018.01.08

Cited by 3 publications

(4 citation statements)

References 33 publications

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“…CEA and CA19-9 are the most common and convenient preoperative serological indicators for colorectal cancer. These markers reflect the occurrence, development, and differentiation of tumor cells and tissues and provide important reference information for clinical diagnosis, classification, and prognosis evaluation ( 31 ). MRI characteristics of rectal cancer combined with CEA and CA19-9 can significantly improve preoperative T and N staging accuracy.…”

Section: Discussionmentioning

confidence: 99%

Extramural vascular invasion nomogram before radical resection of rectal cancer based on magnetic resonance imaging

Tian

Li²,

Xie³

et al. 2023

Front. Oncol.

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PurposeThis study verified the value of magnetic resonance imaging (MRI) to construct a nomogram to preoperatively predict extramural vascular invasion (EMVI) in rectal cancer using MRI characteristics.Materials and methodsThere were 55 rectal cancer patients with EMVI and 49 without EMVI in the internal training group. The external validation group consisted of 54 rectal cancer patients with EMVI and 55 without EMVI. High-resolution rectal T2WI, pelvic diffusion-weighted imaging (DWI) sequences, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were used. We collected the following data: distance between the lower tumor margin and the anal margin, distance between the lower tumor margin and the anorectal ring, tumor proportion of intestinal wall, mrT stage, maximum tumor diameter, circumferential resection margin, superior rectal vein width, apparent diffusion coefficient (ADC), T2WI EMVI score, DWI and DCE-MRI EMVI scores, demographic information, and preoperative serum tumor marker data. Logistic regression analyses were used to identify independent risk factors of EMVI. A nomogram prediction model was constructed. Receiver operating characteristic curve analysis verified the predictive ability of the nomogram. P < 0.05 was considered significant.ResultTumor proportion of intestinal wall, superior rectal vein width, T2WI EMVI score, and carbohydrate antigen 19-9 were significant independent predictors of EMVI in rectal cancer and were used to create the model. The areas under the receiver operating characteristic curve, sensitivities, and specificities of the nomogram were 0.746, 65.45%, and 83.67% for the internal training group, respectively, and 0.780, 77.1%, and 71.3% for the external validation group, respectively.Data conclusionA nomogram including MRI characteristics can predict EMVI in rectal cancer preoperatively and provides a valuable reference to formulate individualized treatment plans and predict prognosis.

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Section: Discussionmentioning

confidence: 99%

Extramural vascular invasion nomogram before radical resection of rectal cancer based on magnetic resonance imaging

Tian

Li²,

Xie³

et al. 2023

Front. Oncol.

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“…While the surgery for all animals was minimally invasive, it was not identical to the planned laparoscopic approach intended in the clinical situation. In clinical trials of macrobeads made from similar agarose and of similar size, but comprised of murine adenocarcinoma cells for the treatment of various cancers, we have used a laparoscopic implant technique that allowed visualization and disbursement of the macrobeads within the peritoneal cavity, as an outpatient procedure 74,75 . Although combined safety and efficacy studies have the benefit of reducing overall numbers of animals in accordance with the 3Rs (replacement, refinement, reduction), a limitation of our combined approach is that experimental manipulation to assess the test article from the efficacy perspective may have influenced safety as it relates to understanding the tissue–macrobead interface.…”

Section: Discussionmentioning

confidence: 99%

Long‐term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

Holdcraft

Graham

Bemrose

et al. 2022

Xenotransplantation

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Although human islet transplantation has proven to provide clinical benefits, especially the near complete amelioration of hypoglycemia, the supply of human islets is limited and insufficient to meet the needs of all people that could benefit from islet transplantation. Porcine islets, secreting insulin nearly identical to that of human insulin, have been proposed as a viable supply of unlimited islets. Further, encapsulation of the porcine islets has been shown to reduce or eliminate the use of immunosuppressive therapy that would be required to prevent rejection of the foreign islet tissue.The goal of the current study was to determine the long-term safety and efficacy of agarose encapsulated porcine islets (macrobeads) in diabetic cynomolgus macaques, in a study emulating a proposed IND trial in which daily exogenous insulin therapy would be reduced by 50% with no loss of glucose regulation. Four of six animals implanted with macrobeads demonstrated ≥ 30% reduction in insulin requirements in year 1 of follow-up. Animals were followed for 2, 3.5, and 7.4 years with no serious adverse events, mortality or evidence of pathogen transmission. This study supports the continued pursuit of encapsulated porcine islet therapy as a promising treatment option for diabetes mellitus.

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“…Many of the gene products induced by the pathway have the capability to induce epithelial-mesenchymal transition (EMT) and promote cell regeneration. , Cancer stem-like cells (CSCs) enable tumor cells to self-renew and undergo unlimited proliferation and differentiation . Studies have shown the presence of rare subpopulations of stem cells within solid tumors that exhibit resistance to chemotherapy or radiotherapy . The high self-renewal ability of CSCs enables them to contribute to tumor recurrence following treatment .…”

Section: Introductionmentioning

confidence: 99%

“… 18 Studies have shown the presence of rare subpopulations of stem cells within solid tumors that exhibit resistance to chemotherapy or radiotherapy. 19 The high self-renewal ability of CSCs enables them to contribute to tumor recurrence following treatment. 20 One of the primary challenge in this field is to identify specific markers that can effectively recognize CSCs.…”

Section: Introductionmentioning

confidence: 99%

BIRC6 Modulates the Protein Stability of Axin to Regulate the Growth, Stemness, and Resistance of Renal Cancer Cells via the β-Catenin Pathway

Zhong,

Wang,

Zhang

et al. 2024

ACS Omega

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The mechanism underlying the development of renal cell carcinoma (RCC) remains unclear, and effective prevention and therapeutic measures are lacking. BIRC6, a protein inhibitor of apoptosis, has attracted great interest. Our data indicated that overexpression of BIRC6 elevated cell growth, colony formation, migration, and invasion of cultured RCC cells, while siRNA knockdown of BIRC6 suppressed these processes. Additionally, BIRC6 was highly expressed in RCC clinical samples along with a downregulated level of Axin. Immunoprecipitation assays found that BIRC6 interacted with Axin and the two proteins colocalized within the cytoplasm of RCC cells. Overexpression of BIRC6 promoted the ubiquitination modification of Axin, while genetic knockdown of BIRC6 suppressed it. Furthermore, overexpression of BIRC6 significantly promoted the turnover of Axin, suggesting BIRC6's inhibitory effect on Axin protein stability. BIRC6 was also upregulated in cancer stem-like cells of RCC and increased the drug resistance of RCC cells against sunitinib. Western blotting assays showed that the overexpression of BIRC6 upregulated CXCR4 protein expression and activated the β-catenin pathway. Two cell lines were then constructed with BIRC6 overexpressed by lentiviruses. Pharmacological administration of a Wnt/β-catenin inhibitor, XAV-939, or genetic knockdown of β-catenin inhibited cell growth, tumor sphere formation, colony formation, migration, and invasion of BIRC6-overexpressed cells. In vivo administration of XAV-939 markedly suppressed the tumorigenesis of BIRC6-overexpressed RCC cells in nude mice. In conclusion, we propose that BIRC6 activates the β-catenin signaling pathway via mediating the ubiquitination and degradation of Axin, promoting the growth, stemness, and drug resistance of RCC cells. This project aims to elucidate the role of BIRC6 as a potential therapeutic target and provide new insights into the clinical treatment of RCC.

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Abstract: The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to mCRC. A phase III clinical trial is planned.

Cited by 3 publications

References 33 publications

Extramural vascular invasion nomogram before radical resection of rectal cancer based on magnetic resonance imaging

Extramural vascular invasion nomogram before radical resection of rectal cancer based on magnetic resonance imaging

Long‐term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

BIRC6 Modulates the Protein Stability of Axin to Regulate the Growth, Stemness, and Resistance of Renal Cancer Cells via the β-Catenin Pathway

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