Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The central theme of this communication is the recognition of an immunodiagnostic potential in a herpes virus antigen, the molecular interrelationship of which with cervical tumor cells is described. In addition to the productive infection caused by herpes simplex virus type 2 (HSV-2) we are confronted by latency and, as suggested by recent studies, by cancer. These different types of virus-host cell interactions are discussed at the host, as well as at the cellular level. A defined level of molecular interaction between host and viral gene products must exist if the virus is to co-exist with the host, as is the case in latency and carcinogenesis. The molecular interpretations posit the presence, in the squamous cervical tumor cells, of a product of the expression of the viral genome that has immunodiagnostic potential. The antigen designated AG-4 fulfills these predictions and appears to have immunodiagnostic potential. AG-4 is present in cervical tumor biopsies, but not in normal cervical tissue. It is a structural component of the HSV-2 virion that, in tissue cultures infected with HSV-2, is synthesized preferentially under conditions that prevent the normal replication of the virus. In view of its structural nature it is most probably virus-coded. AG-4 antibody identified in complement fixation assays with antigen prepared in tissue culture, disappears following successful tumor removal and reappears during cancer recurrence. This antibody also potentially identifies those patients with cervical atypia that are at high risk of neoplastic progression. The clinical benefits of the assay are evident.
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PMID:Immunodiagnostic potential of a virus-coded, tumor-associated antigen (AG-4) in cervical cancer. 19 36

Adjuvant therapy after radical prostatectomy should ideally be limited to those patients at greatest risk for cancer recurrence, but identification of these patients remains a challenge. The local control rate in a group of 7494 patients undergoing radical prostatectomy for patients with pT2a disease of 76% is not different to pN+ disease of 80%. 95% of the pT3 patients were pN+ .90% of them received adjuvant treatment but only few patients with organ-confined cancer. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients with pathologically organ-confined prostate cancer according to risk of progression. Although tumor volume has traditionally been regarded as the most important prognostic factor in patients with localized prostate cancer, a recent multivariate analysis has shown that tumor volume is not an independent predictor. Moreover, accurate measurement of tumor volume is extremely difficult. Preoperative serum PSA levels, clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. Patients with the lowest score had a 92% progression free survival rate at 5 years, compared to only 39% of those with the highest scores. Patients believed to be at higher risk for cancer progression despite having organ confined disease might be targeted for adjuvant therapy and closer surveillance, while those at low risk may be followed less often.
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PMID:[Adjuvant treatment after radical prostatectomy in prostatic carcinoma (pT3 or pTxN+): prognostic factors and results]. 945 84

Mitogenic and growth inhibitory signals influence the activity of a family of cyclin dependent kinases (cdks). p27 is an important cdk inhibitor, acting in G1 to inhibit cyclin-cdks. As negative growth regulators, the cdk inhibitors may function as tumor suppressors. While the p16 gene plays a tumor suppressor role in cancers, p27 gene mutations have been identified only rarely. While high levels of p27 protein are expressed in normal human mammary epithelium, loss of p27 is frequent and is of independent prognostic significance in breast cancers. Low p27 is also a poor prognostic factor in colon, gastric, esophageal, lung, and prostate carcinomas, and enhanced proteasomal degradation may underlie loss of p27 in tumor cells. Loss of p27 has not been significantly correlated with tumor proliferation in a number of studies and may reflect alterations in differentiation and adhesion-dependent growth regulation germane to oncogenesis and tumor progression. Efforts to confirm the prognostic value of p27 are under way in a number of large breast cancer studies. These studies may also indicate whether loss of p27 in association with other traditional or novel markers has greater prognostic potential than each factor alone. p27 immunostaining is inexpensive and reliable and may become part of the routine histopathologic processing of tumors in the near future. Widespread application of p27 in prognostic testing will require greater uniformity in scoring techniques and determination of the cut off levels which distinguish individuals at high and low risk of cancer recurrence and death. Finally, the greatest utility of p27 may lie in the information it sheds on the biology of aberrant growth regulation in breast cancer and the potential to use this in the generation of novel therapeutic strategies.
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PMID:Prognostic implications of expression of the cell cycle inhibitor protein p27Kip1. 1006 70

Cyclin A is required for DNA synthesis during the S phase and progression through the G2/M transition. Increased expression of cyclin A protein has been correlated with poor prognosis in a variety of human tumors. To investigate the possible influence(s) of cyclin A protein on the progression and prognosis of oral squamous cell carcinomas (SCCs) in Taiwan. We examined the expression of cyclin A in oral SCC, epithelial dysplasia (ED) and normal oral mucosa (NOM) by immunohistochemistry using antibodies to cyclin A. Results and Conclusions. The mean labeling indices (LI) in NOM, ED and SCCs were 7.0+/-3.1%, 12.1+/-3.9% and 21.3+/-12.3%, respectively. The cyclin A LI for oral SCCs was significantly higher than that for NOM (P=0.002) or ED (P<0.001). In addition, a high LI for cyclin A was found to correlate with advanced stage (P=0.0048), larger tumor size (P=0.0017), lymph node involvement (P=0.0006) and cancer recurrence (P<0.0001). The Kaplan-Meier analysis showed patients with tumors containing more than 15% cyclin A-positive cells had significantly shorter overall survival than those with tumors containing less than 15% cyclin A-positive cells (P<0.00001). These results indicate that overexpression of cyclin A protein is associated with tumor progression and patient prognosis for oral SCC.
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PMID:Expression of cyclin A is related to progression of oral squamous cell carcinoma in Taiwan. 1274 72

The management of breast cancer in elderly women is controversial. Breast cancer in this age group tends to be biologically less aggressive and is highly responsive to hormonal intervention. The risk of dying of other causes often exceeds the risk of cancer recurrence. For these reasons, older patients tend to be treated less aggressively. One large study of elderly women with breast cancer found that half of the patients were undertreated. Four patients (mean age 72 years, range 61-95 years) underwent a unilateral total mastectomy for cancer under local anesthesia using the tumescent technique of infiltrating dilute lidocaine with epinephrine (25 ml of 1% lidocaine [250 mg] and 1 ml of 1:1000 epinephrine [1 mg] to 1 L of Ringers lactate) via an infusion pump. Three of the patients had estrogen receptor (ER)-negative tumors and one patient had tumor progression despite switching from tamoxifen to anastrozole. All four patients were class IV as defined by the American Society of Anesthesiology (ASA). There was no morbidity related to the surgery in the form of hematoma, wound infection, or skin flap necrosis. The patients were discharged 1-4 days after surgery. The anesthesia was adequate in all four cases and there was no deviation from the described technique. The mean operative time was 35 minutes (range 24-46 minutes). The tumescent technique is a safe, effective method for performing a total mastectomy in patients who would not be considered candidates for general anesthesia.
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PMID:Total mastectomy under local anesthesia: the tumescent technique. 1573 Apr 54

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a fundamental process during cancer progression. Anti-angiogenic strategies have been pursued for cancer treatment and prevention of cancer recurrence and metastasis. Integrins are a family of cell adhesion molecules consisting of two non-covalently bound transmembrane subunits (alpha and beta). Much research has demonstrated that integrin signaling plays a key role in tumor angiogenesis and metastasis. Integrin alphavbeta3 is highly expressed on activated endothelial cells and tumor cells but is not present in resting endothelial cells and most normal organ systems, which makes it a suitable target for anti-angiogenic cancer therapy. In this review we will focus on cancer therapy targeting integrin alphavbeta3 while other integrins (such as alpha5beta1, alphaIIbbeta3, alphavbeta5, alpha6beta4) will only be briefly mentioned when relevant. MEDI-522 (a humanized anti-human integrin alphavbeta3 monoclonal antibody) and Cilengitide (cyclic peptidic integrin alphavbeta3/alphavbeta5 antagonist) are currently in clinical trials for anti-angiogenic cancer therapy. Small interfering RNA (siRNA) that specifically silences integrin alphav and/or beta3 was reported to cause tumor shrinkage in preclinical xenograft models. Combination of anti-integrin alphavbeta3 therapy and other therapeutic approaches (such as chemotherapy, radiotherapy and gene therapy) has also been applied for cancer treatment. Mounting evidence suggests that there is potentially synergistic effect of combined therapeutic approaches over single modality alone. Lastly, integrin targeted delivery (drugs, genes, and radioisotopes) and imaging (optical, MRI, ultrasound, SPECT, and PET) is discussed in detail.
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PMID:Anti-angiogenic cancer therapy based on integrin alphavbeta3 antagonism. 1701 51

Antitumor antigen antibodies are promising tools for cancer therapy, under the judgment of achieving targeted cell destruction. However, antibodies can not only kill tumor cells, but also trigger inflammation in the core of the tumor. Inflammation and cancer have been firmly associated for the last 10 years. Even if this connection was known by intuition since the late 1800s, solid demonstrations of molecular mechanisms behind it have been reported only recently. Nevertheless, basic antiinflammatory factors such as aspirin, and other COX inhibitors, all act somehow as good preventive drugs, but not as therapeutic agents. We have studied the inflammatory pathways associated with tumor cell invasion and metastasis, by analyzing triggers and brittle links in the chain of inflammatory events that promote cancer recurrence and metastasis. In our experiments we observed that signals through TNFalpha and lymphotoxin-alpha (LTalpha) constitute weak links in the tumor-promoting inflammatory scenario. Using gene-targeted mutations, we demonstrated that p55TNF-R blockade could reduce metastasis outcome in mice up to 50%. Likewise, LTalpha blockade reduces mortality in tumor-challenged and untreated mice by 10%, and 54% in mice treated with simple surgical tumor ablation. Conversely, p75TNF-R blockade increases metastasis outcome up to 200%. All taken together these results demonstrate that protumor inflammatory signals transmitted through TNF receptors are not complementary, but opposed: p55TNF-R mediates promalignancy inflammation and p75TNF-R quenches that pathway. Among the triggers of promalignancy inflammatory mechanisms, we demonstrated, that IgGs developed against soluble and shed tumor associated antigens (sTTA) are a major trigger of protumor inflammation. We also demonstrated that by knocking out the B cell receptor (BCR), mice do not develop anti-sTTA IgGs, 90% of mice reject the tumor challenge entirely, and from the 10% that develop tumor, only 20% recur after tumor ablation. Cloning and investigating the IgG-VH sequences, transcribed in lymphocytes and plasma cells, from bone marrow, spleen, and tumor stroma, we also observed that tumor infiltrating plasma cells produce a distinctive family of IgGs. The induction of random expression of these VH peptide sequences in mice, by in vivo transfection into muscle cells, with VH expressing vectors, reduced tumor progression in a significant manner. All these studies indicate that: (1) The use of TNF blockers (such as infliximab and adalimumab) and p55TNF-R blockers (such as lenercept) may have therapeutic benefit in oncology. (2) p75TNF-R blockers (such as etanercept) could be detrimental in oncology. (3) Active or passive immunization against sTAA, such as sTn and others, could be absolutely detrimental in cancer immune therapy. (4) Active or passive humoral immunization against membrane integrated tumor cell antigens should be carefully tested. (5) Investigation of IgG expressed in tumor infiltrating lymphoid cells, could convey important knowledge about the immune responsibility in tumor progression.
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PMID:Antitumor-associated antigens IgGs: dual positive and negative potential effects for cancer therapy. 1716 76

Breast cancer remains a leading cause of morbidity and mortality in women, mainly due to the propensity of primary breast tumors to metastasize to regional and distant sites. Metastatic spread after the removal of a primary tumor can be difficult to identify, creating uncertainty in patients with regards to possible cancer recurrence. This is a particular problem in breast cancer, exemplified by the fact that recurrence can take place after decades of apparent disease-free survival. The mechanisms underlying tumor dormancy in breast cancer remain poorly understood, and this presents significant challenges to both experimental investigation and clinical management of breast cancer. This review will discuss what is currently known about the metastatic process and tumor dormancy, consider the growing evidence that cancer stem cells may contribute to tumor progression and dormancy, and speculate about the clinical importance and implications of this research.
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PMID:Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis. 1747 68

This review summarizes the recent knowledge obtained on the molecular mechanisms involved in the intrinsic and acquired resistance of cancer cells to current cancer therapies. We describe the cascades that are often altered in cancer cells during cancer progression that may contribute in a crucial manner to drug resistance and disease relapse. The emphasis is on the implication of ATP-binding cassette (ABC) multidrug efflux transporters in drug disposition and antiapoptotic factors, including epidermal growth factor receptor cascades and deregulated enzymes in ceramide metabolic pathways. The altered expression and activity of these signaling elements may have a critical role in the resistance of cancer cells to cytotoxic effects induced by diverse chemotherapeutic drugs and cancer recurrence. Of therapeutic interest, new strategies for reversing the multidrug resistance and developing more effective clinical treatments against the highly aggressive, metastatic, and recurrent cancers, based on the molecular targeting of the cancer progenitor cells and their further differentiated progeny, are also described.
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PMID:Recent advances on the molecular mechanisms involved in the drug resistance of cancer cells and novel targeting therapies. 1778 64

Human cancer can arise due to inherited and sporadic genetic and epigenetic changes. These changes consequently inhibit the function of tumor suppressors and pro-apoptotic genes, while activate oncogenes. Most human cancers arise as benign tumors; after acquiring additional genetic and epigenetic changes, they become malignant and eventually metastasize to distal organs. Recent studies have implicated multiple tumor suppressing mechanisms that prevent neoplastic transformation and thus have anti-cancer activities. Among these, cellular senescence has emerged as an important tumorigenesis regulatory mechanism, which not only modulates tumor initiation but also affects tumor progression and maintenance. Cellular senescence is also observed in response to genotoxic chemotherapeutic agents and has been linked to cancer recurrence and drug resistance. Thus improved understanding of regulators of chemotherapy-induced cellular senescence will allow us to explore rational and targeted therapies against various human cancers. In this review, we aim to describe the mechanisms and regulation of three major forms of cellular senescence: replicative senescence (RS), oncogene-induced senescence (OIS) and accelerated cellular senescence (ACS). We also discuss the role of cellular senescence in human cancer and high-throughput genomics-based methods to identify the regulators of cellular senescence. Finally, we highlight aspects of cellular senescence that could be targeted for alternative, yet viable cancer therapies against a variety of human cancers.
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PMID:Exploiting cellular senescence to treat cancer and circumvent drug resistance. 2011 55


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