Novel Cancer Diagnostics: Laser Light Detects Tumors
Learn more. Source: PubMed. Marina Parton. Stan Krajewski. Ian Smith. Maryla Krajewska. Show more authors. Induction of apoptosis is a key factor in the response of tumors to chemotherapy. Laboratory studies have established many of the factors that regulate and execute apoptosis, but the significance of these in human tumors is poorly understood.
Therefore, the relationship between key components of this machinery was examined in primary human breast carcinomas PCR-Analyse der Prostata and 24 h after the initiation of chemotherapy. Apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated nick end labeling assay, and proliferation was assessed using the anti-Ki67 antibody MIB At 24 h after chemotherapy, significant increases in apoptosis and decreases in proliferation were observed, with the degree of increase in apoptosis inversely associated with decrease in proliferation.
The pretreatment biomarker relationships suggest parallel cleavage and activation of these executioner proteins in breast cancer and that XIAP may maintain PCR-Analyse der Prostata survival in the face of caspase PCR-Analyse der Prostata.
The findings provide in vivo evidence in human breast cancer that chemotherapy induces an apoptotic program characterized by up-regulation of Bax and cleavage of caspase substrate DFF Citations References XIAP has the most potent anti-apoptotic effect in cells and is able to inhibit the effector caspases -3,-7 and -9 . Increased expression of XIAP has been shown to be associated with aggressive malignant behaviour and disease progression in lymphoma, breast cancer, lung cancer and renal cell carcinoma   .
Over expression of XIAP has been correlated with poor prognosis for some types of cancer, while converse where either XIAP is not prognostic or high XIAP levels correspond to a longer survival have also been reported . Researchers have also found that XIAP has a dominant contribution to breast cancer progression and chemoresistance .
Recent observations also suggest an important role for XIAP as a key regulator of tumour cell susceptibility to anti cancer drug [8, . Full-text available. Nov Interestingly, XIAP has been shown to be elevated in several malignancies17 18 19, and so has become a promising target in anti-cancer therapies. Gaining a better understanding of how cancer cells evade apoptosis and become resistant to chemotherapy is essential for drug design and the development of novel treatment approaches.
XIAP has been found to be overexpressed in many cancers, including colon cancer17 18 Antagonists or inhibitors of the IAP related proteins may serve as new tools, or indeed exploratory therapeutics , and several XIAP antagonists and SMAC mimetics [34,35] have been described and are advancing into clinical development. One remarkable effect of this class of molecules is their dramatic sensitization of cancer cells to death receptor ligands, such as TNF.
Cytoprotective effects of IAPs revealed by a small molecule antagonist. Nov Biochem J. Deregulated expression of members of the IAP inhibitor of apoptosis family has been identified in a wide variety of neoplastic cells, and synthetic IAP antagonists represent a promising novel class of chemotherapeutic agents.
However, recent studies have shown that IAP antagonists, although primarily designed to target PCR-Analyse der Prostata, trigger ubiquitin-mediated degradation of two related proteins, c-IAP cellular IAP 1 and c-IAP2, PCR-Analyse der Prostata through this process potentiates the death of tumour cells via autocrine cellular-signalling pathways.
In this context, the relative contribution of XIAP as a target of this class of compounds is unclear. These results indicate that IAP antagonists can target multiple IAPs to augment distinct pro-apoptotic signalling pathways, thereby revealing the potential for these compounds in cancer therapy and underscoring the promise of IAP-targeted therapies.
Expression of Bcl-2 and Bcl-x L resulted in cisplatin resistance in various cancer cell lines for example [,]. In patients with ovarian carcinoma, expression of Bcl-x L was associated with a decreased response to platinum chemotherapy , while no association between response and Bcl-2 expression was observed in breast cancer patients . The clinical relevance of XIAP for the response to cisplatin chemotherapy is unclear. In ovarian cancer tissue no association between XIAP expression and response to chemotherapy was found .
An inverse correlation between XIAP expression and pathological response was observed in tissues of advanced bladder cancer patients, however, this was not significant . Cisplatin resistance: Preclinical findings and clinical implications. Dec Biochim Biophys Acta.
Beate Köberle. Cisplatin is used for the treatment of many types of solid cancers. While testicular cancers PCR-Analyse der Prostata remarkably well to cisplatin, the therapeutic efficacy of cisplatin for other solid cancers is limited because of intrinsic or PCR-Analyse der Prostata drug resistance.
Our understanding about the mechanisms underlying cisplatin resistance has largely arisen from studies carried out with cancer cell lines in vitro. Translation of these preclinical findings to the clinic is emerging, but still scarce. The present review describes and discusses the clinical relevance of in vitro models by comparing the preclinical findings to data obtained in clinical studies. However, high proliferation in primary tumours prior to treatment, is often associated with high levels of apoptosis Lipponen et al, ; Lipponen, ; Parton et al, Therefore, ERb expression was investigated with respect to a marker of apoptosis, active caspase-3 Parton et al, No PCR-Analyse der Prostata were detected between ERb isoforms and caspase Expression of oestrogen receptor- in oestrogen receptor- negative human breast tumours.
To analyse the phenotype of breast tumours that express oestrogen receptor- ER alone tissue microarrays PCR-Analyse der Prostata used to investigate if ER isoforms are associated with specific prognostic markers and gene expression phenotypes in ER-negative tumours. This study shows that a range of ER isoform expression occurs in ER-negative breast tumours.
Based on our in vivo observations, ER may have the potential to become a therapeutic target in the specific subcohort of ER-negative PCR-Analyse der Prostata cancers. Keywords: oestrogen receptor- isoforms, breast cancer, immunohistochemistry, proliferation, basal phenotype. Jun Biol Open. Chemokines mediate immune cell trafficking during tissue development, wound healing and infection.
The chemokine CCL2 is best known to regulate macrophage recruitment PCR-Analyse der Prostata wound healing, infection and inflammatory diseases. These data provide novel insight on the mechanisms of chemokine signaling in breast cancer cell growth and invasion, with important implications on targeted therapeutics for anti-cancer treatment.
This article has an associated First Person interview with the first author of the paper. Caspase-3 expression in the MCF-7 human breast cancer cell line caspase-3 def icient revives the apoptotic response. Caspase-3 is also involved in breast cancer apoptosis when cells are exposed to anthracyclines[23,31,32]and cisplatin.
Apoptosis failure is a crucial step in the initiation and progression of cancer. High apoptotic rates have been reported in invasive cancers compare to the paired normal rates . We found no significant difference between procaspase-3 and active caspase-3 expression in triple negative GBC. Expression of procaspase 3 and activated caspase 3 and its relevance in hormone-responsive gallbladder carcinoma chemotherapy.
Sep Kor J Intern Med. The higher incidence of gallbladder cancer GBC in females has been accredited to the involvement of hormones.
The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases such as caspase, etc. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis which directly correlated with the level PCR-Analyse der Prostata active caspase-3 in hormone-responsive GBC.
We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies. Caspase 3 in breast cancer. An inability to undergo apoptosis is widely thought to contribute to both tumorigenesis and tumor progression.
One of the key mediators of apoptosis PCR-Analyse der Prostata the thiol protease caspase 3. In this investigation, caspase 3 mRNA and protein expression in breast cancer was examined. Caspase 3 was measured at the mRNA PCR-Analyse der Prostata using reverse transcription-PCR and at the protein level using both Western blotting and PCR-Analyse der Prostata assays.
We conclude that rates of apoptosis as measured by both caspase 3 activation and nucleosome PCR-Analyse der Prostata are higher in breast cancer than in nonmalignant breast tissue. This finding would appear to conflict with the widely held belief that apoptosis is reduced in malignancy.
The proliferation:apoptosis ratio, however, may be higher in carcinomas than in the corresponding normal tissue. The discrepancy with our results may be explained by the fact that the combination PCR-Analyse der Prostata cytotoxic drugs cisplatin, epirubicin and 5-fluoro- uracilPCR-Analyse der Prostata and schedule of administration to the patients were different.
Parton et al. It is interesting to note that we observed nuclear expression of Bax in some of the breast cancer samples; this unusual localization has previously been observed in cultured cells including human breast cancer cells Nishita PCR-Analyse der Prostata al.
Prognostic value of Bcl-2 in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy. Jul An unusual nuclear localization of Bax was observed in some biopsies, but this localization did not correlate with the tumor response or outcome of the patients. We found that a high Bcl-2 expression had no predictive value but had prognostic value in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy. This may be measured by morphologic criteria using standard microscopic techniques, but it is more often measured in vivo by application of the TUNEL TdT-mediated dUTP-biotin nick end labeling methodology that PCR-Analyse der Prostata biotinylated nucleotides to the enormous number of DNA strand ends created during late-stage apoptosis.
The immunohistochemical staining of components of the execution machinery of apoptosis, PCR-Analyse der Prostata as activated caspase 3, have been assessed as surrogates for PCR-Analyse der Prostata itself with variable success [3, PCR-Analyse der Prostata.