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Pubmed
Journal: Human reproduction (Oxford, England)
December/20/2004
Abstract

Despite reasonable achievements in different animal species, the debate about many technical aspects of ovarian tissue banking is continuing. Human ovarian tissue banks are increasingly established around the world without a clear plan about how to make the best use of such tissue. One of the important challenges facing this growing technology is to determine the ideal method for the use of this cryopreserved ovarian tissue. It is not uncommon in medicine to introduce a technology without a clear understanding of the consequences. If it is decided that ovarian tissue is to be autotransplanted, what is the most suitable place? Which technique should be implemented? As a part of the ongoing debate on ovarian tissue banking in cancer patients, this paper supports the notion that cryopreservation of an intact ovary with its vascular pedicle may be a viable alternative to the currently available techniques. Research in the development of technology to cryopreserve whole organs as well surgical techniques for the auto-transplantation of an ovary with its vascular pedicle should be encouraged.

Pubmed
Journal: Journal of immunotherapy (Hagerstown, Md. : 1997)
November/21/2004
Abstract

We present a novel vascular tumor therapy approach based on lysing endothelial cells by cytotoxic T lymphocytes (CTLs). Retargeting of CTLs is achieved by a recombinant bispecific antibody molecule (bispecific single-chain diabody) directed against human endoglin (CD105, EDG) and the T-cell coreceptor CD3 (scDb EDGCD3). Bacterially expressed scDb EDGCD3 was able to bind to endoglin-expressing endothelial cells as well as CD3-expressing T lymphocytes. The single-chain diabody mediated killing of endothelial cells (HUVEC, HMEC) by activated cytotoxic T lymphocytes at picomolar concentrations, and cells not expressing endoglin were not affected. Because endoglin is up-regulated in the vasculature of many solid tumors, this antibody molecule should be capable of lysing tumor endothelial cells and thus destroying the vascular bed of the tumor.

Pubmed
Journal: Nature
October/18/2015
Pubmed
Journal: Drug metabolism and drug interactions
March/9/2014
Abstract

BACKGROUND

The discovery of cisplatin's antitumor activity led to a great interest in the potential application of coordination compounds as chemotherapeutic agents. It is essential to identify new compounds that selectively inhibit tumor proliferation, evading secondary effects and resistance associated with chemotherapeutics.

METHODS

The in vitro antiproliferative potential of an organotin(IV) compound was evaluated using colorectal and hepatocellular carcinoma, mammary gland adenocarcinoma cell lines, and human fibroblasts. Tumor cell death was evaluated by fluorescence microscopy and flow cytometry for the Sn(IV) compound and also for a Co(II) compound bearing 1,10-phenanthroline-5,6-dione as ligand. Comparative proteomic analysis for both compounds was assessed in the colorectal cancer cell line.

RESULTS

The Sn(IV) compound presented a high cytotoxic effect in colorectal and hepatocellular carcinoma cell lines (IC50 of 0.238 ± 0.011 μM, 0.199 ± 0.003 μM, respectively), and a lower cytotoxicity in human fibroblasts. Both compounds induced cell apoptosis and promoted the overexpression of oxidative stress-related enzyme superoxide dismutase [Cu-Zn] (SODC). The Co(II) compound induced a decreased expression of anti-apoptotic proteins (translationally-controlled tumor protein and endoplasmin), and the Sn(IV) compound decreased expression of proteins involved in microtubule stabilization, TCTP, and cofilin-1.

CONCLUSIONS

Our data reveals a high in vitro antiproliferative potential against cancer cell lines and a moderate selectivity promoted by the Sn(IV) compound. Proteomic analysis of Sn(IV) and Co(II) compounds in the colorectal cancer cell line allowed an insight to their mechanisms of action, particularly by affecting the expression of proteins typically deregulated in cancer, and also suggesting a promising therapeutic potential for both compounds.

Pubmed
Journal: Clinical oncology (Royal College of Radiologists (Great Britain))
February/6/2014
Pubmed
Journal: Cancer
May/22/2017
Abstract

BACKGROUND

Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA).

METHODS

Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0 < 0.2), prefrail (cutoff value, 0.2 < 0.35), and frail (cutoff value, ≥ 0.35) groups.

RESULTS

Two hundred and fifty patients (50%) were nonfrail, 197 (39%) were prefrail, and 52 (11%) were frail. Older patients (aged ≥ 80 years) and those who had lower education, were living alone, and had higher stage disease were associated with prefrail/frail status. Prefrail/frail patients were more likely to have grade ≥3 toxicity but not to have a dose delay or reduction, and they were more likely to discontinue drug and be hospitalized. The association with grade ≥3 toxicity was attenuated by controlling for a toxicity risk calculator, but the other outcomes were not.

CONCLUSIONS

A deficit-accumulation frailty index can be constructed from a CGA in older patients with cancer and can indicate the frailty status of the population. The frailty status so determined is associated both with outcomes likely because of chemotherapy toxicity and with those likely because of age-related physiologic and functional deficits and thus can be useful in the overall assessment of the patient. Cancer 2016;122:3865-3872. © 2016 American Cancer Society.

Pubmed
Journal: Future oncology (London, England)
October/18/2016
Abstract

BACKGROUND

We performed a meta-analysis of the risk of endocrine adverse events associated with immune check point inhibitors.

METHODS

Eligible studies included randomized trials of cancer patients on immune checkpoint inhibitors; describing events of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency.

RESULTS

A total of ten clinical trials were eligible for the meta-analysis. The relative risk of all-grade hypothyroidism, hyperthyroidism, hypophyisitis and adrenal insufficiency were 8.26 (95% CI: 4.67-14.62; p < 0.00001), 5.48 (95% CI: 1.33-22.53; p = 0.02); 22.03 (95% CI: 8.52-56.94; p < 0.00001), 3.87 (95% CI: 1.12-13.41; p = 0.03), respectively.

CONCLUSIONS

Our meta-analysis has demonstrated that the use of immune check point inhibitors is associated with an increased risk of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency compared with control.

Pubmed
Journal: Cancer treatment reviews
January/29/2017
Abstract

The study of cancer stem cells (CSCs) has shown that tumors are driven by a subpopulation of self-renewing CSCs that retain the capacity to engender the various differentiated cell populations that form tumors. The characterization of CSCs has indicated that CSCs are remarkably resistant to conventional radio- and chemo-therapy. Clinically, the remaining populations of CSC are responsible for metastasis and recurrence in patients with cancer, which can lead to the disease becoming chronic and incurable. Therefore, the elimination of CSCs is an important goal of cancer treatments. Furthermore, CSCs are subject to strong regulation by the surrounding microenvironment, which also impacts tumor responses. In this review, we discuss the mechanisms by which pathways that are defective in CSCs influence ultimately therapeutic and clinical outcomes.

Pubmed
Journal: The Analyst
January/3/2017
Abstract

Cancer is currently one of the top non-communicable human diseases, and continual research and developmental efforts are being made to better understand and manage this disease. More recently, with the improved understanding in cancer biology as well as the advancements made in microtechnology and rapid prototyping, microfluidics is increasingly being explored and even validated for use in the detection, diagnosis and treatment of cancer. With inherent advantages such as small sample volume, high sensitivity and fast processing time, microfluidics is well-positioned to serve as a promising platform for applications in oncology. In this review, we look at the recent advances in the use of microfluidics, from basic research such as understanding cancer cell phenotypes as well as metastatic behaviors to applications such as the detection, diagnosis, prognosis and drug screening. We then conclude with a future outlook on this promising technology.

Pubmed
Journal: Clinical reviews in allergy & immunology
February/1/2017
Abstract

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases (collectively known as myositis) affecting the skeletal muscles as well as other organ systems such as skin, lungs, and joints. The primary forms of myositis include polymyositis (PM), dermatomyositis (PM), and immune-mediated necrotizing myopathy (IMNM). Patients with these diseases experience progressive proximal muscle weakness, have characteristic muscle biopsy findings, and produce autoantibodies that are associated with unique clinical features. One distinguishing feature of these patients is that they are also known to have an increased risk of cancer. Since the first description of the association in 1916, it has been extensively reported in the medical literature. However, there have been significant variations between the different studies with regard to the degree of cancer risk in patients with IIM. These discrepancies can, in part, be attributed to differences in the definition of malignancy-associated myositis used in different studies. In recent years, significant advances have been made in defining specific features of IIM that are associated with the development of malignancy. One of these has been myositis-specific antibodies (MSAs), which are linked to distinct clinical phenotypes and categorize patients into groups with more homogeneous features. Indeed, patients with certain MSAs seem to be at particularly increased risk of malignancy. This review attempts a systematic evaluation of research regarding the association between malignancy and myositis.

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