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)

Between May 1977 and August 1989, 357 patients (199 male, 158 female; median age 40 years) with highly anaplastic astrocytomas other than glioblastoma multiforme were treated according to any of several protocols used in studies by the University of California, San Francisco, and the Northern California Oncology Group. The data evaluated were age, Karnofsky Performance Score, survival, time to tumor progression, therapy, and the effect of treatment at the time of progression. The records of 219 patients were taken from the University of California database, and those of the other 138 were taken from the Northern California Oncology Group computer files. Their median Karnofsky Performance Score was 90% (range 40-100%), the overall median survival was projected as 170.9 weeks, and the median time to first tumor progression was 127.3 weeks. The median survival time measured after the first progression was 41.3 weeks. Age and Karnofsky Performance Score had a significant influence on survival and on time to the first tumor progression, whereas extent of surgery and the use of interstitial brachytherapy in the initial therapy did not. We conclude that these patients can expect a median survival of over 3 years, that young age and high Karnofsky Performance Score have a positive influence on survival, and that salvage therapies can extend survival after the onset of tumor progression for nearly a year. Although it did not lengthen survival when used in initial therapy, interstitial brachytherapy used at the time of tumor progression was associated with increased survival.
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PMID:Highly anaplastic astrocytoma: a review of 357 patients treated between 1977 and 1989. 157 29

Treatment results for 36 patients with juvenile pilocytic astrocytoma treated from 1942 through 1985 at the University of California, San Francisco, were reviewed. Twenty-two tumors were located in the posterior fossa, 10 were in the hypothalamic region, and four were in the cerebral hemispheres. Twenty-eight patients were less than 18 years of age. The overall survival rate was 83% and 70% at 10 and 20 years, respectively. All 12 patients who had total tumor resection remain disease-free; only two of the 12 received postoperative irradiation. The 10- and 20-year freedom-from-progression for the 19 patients who had incomplete resection and received at least 40 Gy of postoperative irradiation was 74% and 41%, respectively. All patients who failed treatment had local recurrence. One patient developed diffuse meningeal seeding, after four local recurrences in the posterior fossa over a 23-year period. Six patients failed treatment and had a repeat biopsy at the time of recurrence or at postmortem examination, and three showed histological progression of the tumor to an anaplastic astrocytoma. Based on this study and others in the literature, a protocol has been adopted whereby patients who have total tumor resection are not treated with postoperative irradiation. Patients who have incomplete tumor resection and are older than 3 years of age are currently treated with postoperative partial-brain irradiation, to a dose of 45 to 60 Gy. In general, young children with incomplete resection are followed closely with computerized tomography or magnetic resonance imaging and are treated with chemotherapy or irradiation if tumor progression is documented.
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PMID:Treatment results of juvenile pilocytic astrocytoma. 339 63

The records of 124 patients treated for acoustic neurilemoma at the University of California, San Francisco, from 1945 through 1983 were reviewed. Patients were classified by the extent of surgical resection: total, nearly total (90% to 99% resection), subtotal (less than 90% resection), or biopsy. Thirty-one patients received irradiation as part of their primary treatment. Total resection of tumor, without irradiation, was associated with a 3% chance of local recurrence. One of 15 patients who had nearly total resection of their tumor and did not receive postoperative irradiation suffered a recurrence, compared with neither of the two patients who received postoperative irradiation (greater than 45 Gy) following nearly total resection. Postoperative irradiation (greater than 45 Gy) decreased the recurrence rate after subtotal resection from 46% (six of 13 cases without irradiation) to 6% (one of 17 cases: p = 0.01). All three patients treated by biopsy alone received postoperative irradiation (greater than 45 Gy), and none had a recurrence. Six patients were treated with preoperative irradiation because of excessive tumor vascularity; four are without evidence of disease 12 to 23 years later. Only three of seven patients treated with irradiation for tumor recurrence after surgical resection survived. It is concluded that postoperative irradiation significantly decreased the chance for local tumor progression following subtotal resection of acoustic neurilemoma, and that postoperative irradiation may be effective therapy following treatment by biopsy. Patients with total or nearly total resection appeared not to benefit from postoperative irradiation.
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PMID:Efficacy of irradiation for incompletely excised acoustic neurilemomas. 368 24

Forty-five children harboring brain-stem tumors were treated at the University of California, San Francisco, between 1969 and 1979. Pathological diagnoses were made in 19 patients. All patients received radiation therapy (RT). Thirteen patients received chemotherapy before, during, or immediately after RT. Twenty-four patients were treated with chemotherapy at the time of tumor progression, after initial treatment with RT alone. No statistically significant difference in time to tumor progression or survival was found for treatment with chemotherapy as an adjuvant to RT compared to treatment with RT alone followed by chemotherapy administered at the time of tumor progression. There were, however, more long-term survivors in the group that was first treated with chemotherapy at the time of tumor progression. There was no statistically significant correlation between survival and tumor pathology or location, although there were more long-term survivors among patients harboring low-grade gliomas and among patients with tumors confined to the midbrain. The authors documented the response of some brain-stem tumors to chemotherapy; however, cooperative controlled studies will be required to determine the optimum treatment for this disease.
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PMID:Chemotherapy of pediatric brain-stem tumors. 626 50

The overexpression of HER2, a transmembrane glycoprotein tyrosine kinase, has been implicated in mitogenesis, cell survival, invasion and angiogenesis. Preclinical evidence suggests that HER2 overexpression contributes to tumor progression in non-small cell lung cancer (NSCLC) and retrospective clinical correlative studies show that it is probably associated with poor clinical outcome. Trastuzumab (Herceptin, Genentech Inc., South San Francisco, CA) is a recombinant humanized monoclonal antibody that targets HER2 and is currently approved for use in the treatment of patients with HER2-overexpressing metastatic breast cancer. Two primary mechanisms proposed for the activity of trastuzumab are downregulation of HER2 and induction of antibody-dependent cell-mediated cytotoxicity. Evidence from preclinical studies of trastuzumab in NSCLC and other cell lines, the presence of HER2 overexpression in NSCLC clinical specimens and the clinical benefit derived from trastuzumab in phase II and III metastatic breast cancer trials have led to the development of clinical trials of trastuzumab in NSCLC. Phase II studies of trastuzumab in patients with stage IIIB or IV NSCLC are being conducted to test the efficacy of trastuzumab as a single agent or in combination with chemotherapy. Preliminary results show combinations of chemotherapy plus trastuzumab are well tolerated, with encouraging response rates of 21-40%. A randomized phase II trial of chemotherapy with or without trastuzumab showed promise in a small subgroup of patients with 3+ HER2 overexpression by immunohistochemistry or HER2 DNA amplification by fluorescence in situ hybridization. Taken together, these data indicate that trastuzumab warrants further investigation in a clinical study in selected patients with NSCLC.
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PMID:Non-small cell lung cancer clinical trials with trastuzumab: their foundation and preliminary results. 1205 63

53 histological slides obtained from 4 patients aged 35-68 years with diagnosis of uterine carcinoma without invasion (16 patients) and tumor invasion into uterine muscular membrane (24 patients) were retrospectively analyzed. On the basis of morphometry and ploidometry of 2989 nuclei on the image analyzer Imager-CG (Russia) with a computer program Avtan-San, a complex of diagnostic criteria characterizing the grade of malignancy of uterine tumors was obtained. Differential diagnostic ploidometric characteristics of 4 degrees of tumor progression are described. With the process intensification the amount of genetic material in tumor cell nuclei increase 1.7-fold, proliferative activity 2.2-fold, number of polyploid cells--1.5-fold. These data specify the degree of differentiation of uterine body adenocarcinoma and help to plan treatment policy for patients with uterine carcinoma.
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PMID:[Morphometric characteristics (assessment of ploidy) of the degree of differentiation of uterine body adenocarcinoma]. 1253 24

Bevacizumab (Avastin; Genentech, Inc.; South San Francisco, CA) is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, a key regulator of tumor angiogenesis. Bevacizumab demonstrated potent antitumor activity in preclinical models and has also shown biologic activity and clinical benefit in clinical studies. Notably, a randomized, placebo-controlled phase II trial in renal cell carcinoma demonstrated a significantly longer time to tumor progression with bevacizumab monotherapy. Furthermore, in a phase III trial for untreated advanced colorectal cancer, the addition of bevacizumab to chemotherapy led to significantly longer overall survival and progression-free survival times than chemotherapy alone. The clinical development of bevacizumab has been expanded to include confirmatory phase III trials and exploratory phase II trials in a variety of solid tumors and hematologic malignancies. Treatment regimens being examined include bevacizumab alone and in combination with conventional chemotherapy, radiation, immune therapy, and biologically targeted agents.
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PMID:Expanding the clinical development of bevacizumab. 1517 13

An inaugural conference in Tucson Arizona on May 6-9, 2004 brought together more than 70 clinical and basic scientists to discuss recent research advances in understanding and targeting the progression of the human prostate cancer. The informal meeting was unique in that it provided the opportunity for discussion and interaction between these different groups of scientists whose paths rarely cross. The goal of the meeting was to develop new and novel approaches in understanding the human prostate cancer in order to uncover therapeutic targets. Faculty from six different cancer centers were represented including Memorial Sloan-Kettering Cancer Center (New York, NY); Arizona Cancer Center (Tucson, AZ); Fred Hutchinson Cancer Center (Seattle, WA); Chao Family Comprehensive Cancer Center (Irvine, CA); the Sydney Kimmel Cancer Center (San Diego, CA); Jonsson Comprehensive Cancer Center, University of California (Los Angeles, CA); and University of Massachusetts Memorial Cancer Center (Worcester, MA). Several important concepts emerged from this meeting as a result of the basic and clinical science interface. These concepts include: (1) Human prostate cancer has unique biological features as compared to other human epithelial malignancies; (2) Tumor plasticity is evident early in prostate cancer progression as evidenced by alterations in the extracellular matrix; (3) New therapeutic strategies should include the co-targeting of the stroma and prostate cancer; (4) Cell-cell and cell-ECM adhesion switching are reversible phenotypes evident early in human prostate tumor progression; (5) The discovery of molecular signatures including genomic or proteomic patterns for the discrimination of indolent versus aggressive disease is a potentially powerful tool and requires multifactorial approaches for success; and (6) New biomarkers and innovative tissue specific imaging modalities for human prostate cancer are being developed that may aid in a more accurate assessment of prostate cancer in patients.
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PMID:Therapeutic targeting of prostate cancer. 1553 35

Angiogenesis is critical for normal and pathologic processes in new blood vessel formation. A recent significant advance in the treatment of metastatic colorectal cancer has occurred by the development of agents targeting key regulatory molecules involved in this process, specifically vascular endothelial growth factor (VEGF). These angiogenesis inhibitors, include bevacizumab (Avastin, Genentech, Inc, South San Francisco, CA), which binds free VEGF. Recently, a phase III, multicenter, double-blind, randomized, placebo-controlled trial was designed to determine whether or not the addition of bevacizumab to first-line irinotecan, 5-fluorouracil, and leucovorin chemotherapy was completed in patients with metastatic colorectal cancer. The trial showed a higher response rate, longer time to tumor progression, and prolonged overall survival in patients with metastatic colorectal cancer. Of note, this was the first large, randomized, phase III study to show the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Other potential targets of angiogenesis, such as the VEGF receptor and multi-targeted agents, are undergoing evaluation in clinical trials.
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PMID:Angiogenesis inhibitors in the treatment of colorectal cancer. 1569 25

Targeted molecular therapeutics are tailored toward the genetic abnormalities that cause tumor progression. Modulation of certain signaling pathways that are aberrant in cancer cells has the potential to provide an effective, nontoxic approach to therapy in a broad range of cancers. Agents targeting BCR-ABL (imatinib mesylate [formerly known as STI-571], Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ), retinoid receptor fusion proteins (all-trans retinoic acid), ErbB-2 or HER2/neu (trastuzumab, Herceptin; Genentech, Inc, South San Francisco, CA), epidermal growth factor receptor (IMC-C225 and ZD1839), and the phosphatidylinositol 3-kinase pathway (CCI-779) have all induced remarkable, nontoxic responses in a subset of patients with cancer and abnormalities in the corresponding signal transduction cascades. To achieve successful individualized therapy, the specific components within the aberrant signaling pathways that are driving the pathophysiology of the tumors must be identified in each patient. Molecular diagnostics can identify patients in whom the target is aberrant; linking molecular diagnostics with effective molecular therapeutics will be necessary to translate these concepts into approaches that will alter the outcome for patients with cancer. In addition, intermediary markers and/or molecular imaging techniques must be used to identify the biologically relevant dose that is sufficient to inhibit the target of interest. This review focuses on the P13K pathway, and novel molecules targeting this pathway, to illustrate the questions and challenges underlying the implementation of molecular therapeutics in breast and ovarian cancer.
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PMID:Mammalian target of rapamycin. 1579 39


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