Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over several decades, in vitro experimental studies have demonstrated that retinoids effect the process of carcinogenesis and tend towards the alteration of cells back to more normal differentiation. This hypothesis has formed the basis of several chemopreventive studies in breast cancer, cervical cancer, head and neck cancer and lung cancer. Experimental evidence exists to suggest that chemoprevention with retinoids may well have a beneficial effect in patients at high risk of acquiring prostate cancer. None of the studies, however, in any of the cancers have yet been definitive, but opportunities exist with newer retinoids that appear to be able to be given on a long-term basis with minimal toxic side effects, to explore this exciting potential treatment pathway.
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PMID:Retinoids in chemoprevention. 1032

On returning from a medical meeting, we learned that sadly a patient, "Mr. B.," had passed away. His death was a completely unexpected surprise. He had been doing well nine months after a course of intensive radiotherapy for a locally advanced head and neck cancer; in his most recent follow-up notes, he was described as a "complete remission." Nonetheless, he apparently died peacefully in his sleep from a cardiac arrest one night and was found the next day by a concerned neighbor. In our absence, after Mr. B. expired, his death certificate was filled out by a physician who didn't know him in detail, but did know why he recently was treated in our department. The cause of death was listed as head and neck cancer. It wasn't long after his death before we began to receive those notorious "requests for additional information," letters from the statistical office of a well-known cooperative group. Mr. B., as it turns out, was on a clinical trial, and it was "vital" to know further details of the circumstances of his passing. Perhaps this very large cancer had been controlled and Mr. B. succumbed to old age (helped along by the tobacco industry). On the other hand, maybe the residual "fibrosis" in his neck was actually packed with active tumor and his left carotid artery was finally 100% pinched off, or maybe he suffered a massive pulmonary embolism from cancer-related hypercoagulability. The forms and requests were completed with a succinct "cause of death uncertain," adding, "please have the Study Chairs call to discuss this difficult case." Often clinical reports of outcomes utilize and emphasize the endpoint "disease specific survival" (DSS). Like overall survival (OS), the DSS can be calculated by actuarial methods, with patients who have incomplete follow-up "censored" at the time of last follow-up pending further information. In the DSS, however, deaths unrelated to the index cancer of interest are censored at the time of death; thus, a death from intercurrent disease is considered a "success" (to the investigator, that is; obviously, not to the patient and his or her family). The DSS rate will always be superior to the OS rate. Obviously, for any OS curve, if one waits long enough it will ultimately come to zero. There is thus a very logical rationale for reporting the DSS separately, particularly in diseases where death from intercurrent disease is expected to be common. Analyzing the DSS allows researchers to better compare the biologic efficacy of two or more cancer treatments, since it does not necessarily come to zero. Unlike some other endpoints, including local-regional control or freedom from progression, it takes into account the possibility of salvage therapy. DSS also focuses on an endpoint of interest to the public-death from cancer. In a recent popular media survey in which people were asked how they would choose to die if they could, 0% selected cancer. However, there are two serious potential problems with heavy dependence on the DSS. First, since patients who die from intercurrent disease are considered "cured," it seriously inflates the apparent effectiveness of a cancer treatment. Given the same biologic disease and the same treatment, the DSS as calculated in an old, sick population at high risk of intercurrent death will be better than the DSS in a younger, healthier population whose major risk is from their cancer. This problem has been discussed with respect to early stage prostate cancer, in which the conservative approach of observation has been criticized. The studies at issue rely heavily on the DSS, suggesting a comparable DSS (90% at 10 years) with "watchful waiting" to other researchers' results with aggressive therapy. The problem is that these series of conservative management focus on a patient population (as opposed to individuals) with a high risk of competing causes of mortality, which is very different from the population of patients generally treated with aggressive therapy (in which some have shown overall survivals superior to age-matched controls). It is fallacious and illogical to compare nonrandomized series of observation to those of aggressive therapy. In addition to the above problem, the use of DSS introduces another potential issue which we will call the bias of cause-of-death-interpretation. All statistical endpoints (e.g., response rates, local-regional control, freedom from brain metastases), except OS, are known to depend heavily on the methods used to define the endpoint and are often subject to significant interobserver variability. There is no reason to believe that this problem does not occasionally occur with respect to defining a death as due to the index cancer or to intercurrent disease, even though this issue has been poorly studied. In many oncologic situations-for example, metastatic lung cancer-this form of bias does not exist. In some situations, such as head and neck cancer, this could be an intermediate problem (Was that lethal chest tumor a second primary or a metastasis?.Would the fatal aspiration pneumonia have occurred if he still had a tongue?.And what about Mr. B. described above?). In some situations, particularly relatively "good prognosis" neoplasms, this could be a substantial problem, particularly if the adjudication of whether or not a death is cancer-related is performed solely by researchers who have an "interest" in demonstrating a good DSS. What we are most concerned about with this form of bias relates to recent series on observation, such as in early prostate cancer. It is interesting to note that although only 10% of the "observed" patients die from prostate cancer, many develop distant metastases by 10 years (approximately 40% among patients with intermediate grade tumors). Thus, it is implied that many prostate cancer metastases are usually not of themselves lethal, which is a misconception to anyone experienced in taking care of prostate cancer patients. This is inconsistent with U.S. studies of metastatic prostate cancer in which the median survival is two to three years. It is possible that many deaths attributed to intercurrent disease in "watchful waiting" series were in fact prostate cancer-related, perhaps related to failure to thrive, urosepsis, or pulmonary emboli. We will not know without an independent review of the medical records of individual patients; in some cases, even the most detailed review, sometimes even an autopsy, will not be conclusive. There are only a few data available describing the problems created by cause-of-death-interpretation bias. One small study, presented only in abstract form, assessed the cause of death in 50 randomly selected prostate cancer patients who died. Five experts in prostate cancer were asked to assign the cause of death as due to or not due to prostate cancer. The DSS varied from 21% to 35% among the five reviewers, a relative difference of 66%. Studies of autopsies, which are now rarely done in the U.S., have shown that fatal malignant tumors were occasionally missed by clinicians and-even more sobering-an occasional patient thought to have died from metastatic cancer is found to have no tumor but to have died from a "benign" cause such as TB. One study suggested an error rate of approximately 8%. Clearly the use of DSS is here to stay and is a useful adjunct to OS in analyzing randomized trials. There needs to be more research on the validity and interobserver reproducibility of the DSS. In the meantime, researchers should not report DSS without reporting OS and the reasons for intercurrent deaths should be described-peer reviewers should enforce this. As with so many other problems with statistics in the medical literature, it is the job of the reader to remain skeptical. The rate of intercurrent deaths in a study should reflect the age and demographics of the study population. If the DSS is far superior to the OS, the population being studied may be unusually sick (and thus unrealistic), or there may be a bias in classifying the causes of death. Similarly, if the DSS and OS are identical (unless a highly virulent malignancy is being studied), it may suggest the researchers have only included an unusually healthy (and thus unrealistic) patient population. Finally, we would also be a bit suspicious of a sizeable series that did not have any deaths that were considered of "uncertain" cause, unless the researchers specifically included them as being due to the cancer. We honestly think that everybody has a few patients like Mr. B.
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PMID:"Just Another Statistic" 1038 5

Since early 1997, dynamic multileaf collimators (DMLCs) have been used in our division for intensity modulated radiotherapy (IMRT). We have used IMRT to: irradiate concave targets (head and neck, paraspinal tumors); combine beams with shallow hinge angles (mediastinum, lung tumors); deliver intentionally inhomogeneous dose distributions (prostate, paranasal sinuses, brain tumors). IMRT is now our standard treatment for locoregional relapse (after high-dose radiotherapy) for head and neck cancer and for radical treatment of localized prostate cancer. For a variety of other tumors, conventional 3D-plans are compared with IMRT-plans, the latter being clinically implemented if superior. We developed a geometry based IMRT planning strategy to create assemblies of static intensity modulated (IM)-beams which consist of uniform (unmodulated) segments. By a translator program, segments are combined in a single prescription which allows delivery under computer control. Cost-containment is further improved by automation of the planning. After manual or semi-automated contouring of PTV and the organs at risk, prostate IMRT plans, based on a class solution, are generated and optimized by a computer. IMRT for pharyngeal relapses and most other tumor sites is planned semi-automatically. IMRT replaces gradually conventional treatments in our division. Interesting dose distributions generated by IMRT allow a better sparing of normal tissues with decreased acute and late toxicity, and offer a window for further dose escalation.
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PMID:[Intensity modulated radiotherapy with dynamic multileaf collimator. Technique and clinical experience]. 1057 8

Despite the introduction of screening procedures and an increased public awareness of prostate cancer, a substantial number of patients present with locally advanced prostate cancer. Traditional therapies (such as radiation therapy or radical prostatectomy) applied either alone or in combination fail to control local disease in a large number of cases and have no effect on disseminated disease. Recent advances in molecular oncology and genetics have led to such novel therapies as p53 gene therapy, which we are currently evaluating in a clinical protocol in patients with locally advanced (nonmetastatic) prostatic cancer. Ad5CMVp53 (RPR/INGN 201) has previously shown promise in both patients with lung cancer and those with head and neck cancer. The traditional end points used to appraise prostate cancer preclude rapid evaluation of the patient's disease and prevent modification of the therapeutic strategy, and we suggest that the pathologic stage after therapy be evaluated as an intermediate end point.
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PMID:Ad5CMVp53 gene therapy for locally advanced prostate cancer--where do we stand? 1085 46

Taxol was introduced for the clinical treatment of several solid tumor malignancies in the 1990s. It has been established that primary chemotherapy based on Taxol is the standard for non-small cell lung cancer and epithelial ovarian cancer. After initial chemotherapy containing doxorubicin, sequential administration of Taxol for advanced or metastatic breast cancer is recommended by the Food and Drug Administration in the United States. Taxol-based chemotherapy and/or concurrent chemoradiation for head and neck cancer, esophageal carcinoma, urothelial and prostate cancer are under investigation, but these trials have not produced evidence showing that they are superior to the present standard treatment for these malignancies. Although phase I/II trials of Taxol combined with new agents such as vinorelbine, topotecan, CPT-11 and others may demonstrate efficacy to a certain extent for some solid tumor malignancies, a phase III study will be required in the next stage. Taxol combined with other agents focusing on molecular targets will be an important approach in next decade. Inhibition of signal transduction by a noncytotoxic agent such as herceptine has the potential to enhance the cytotoxic effect of Taxo.
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PMID:[Evidenced-based medicine and future direction of Taxol]. 1094 27

The adenovirus 5 early region 1A (E1A) can function as a tumor suppressor gene and is being used in clinical trials as a therapeutic agent for advanced breast, ovarian, and head and neck cancer. Recently, there has been a dispute regarding whether transfection with the E1A gene can induce expression of the Ewing sarcoma oncogenic fusion transcript EWS-FLI1 (Sanchez-Prieto et al., Nat. Med., 5: 1076-1079, 1999; Melot and Delattre, Nat. Med., 5: 1331, 1999; Kovar et al., Cancer Res., 60: 1557-1560, 2000). In an effort to settle the controversy, we tested several stable E1A transfectants of cell lines MDA-MB-231, MCF-7, MDA-MB-435 (breast cancer), SKOV3-ipl (ovarian cancer), and PC-3 (prostate cancer), as well as parental and vector-transfected controls, HEK 293 cells, and RD-ES (Ewing sarcoma) cells, for the EWS-FLI1 fusion product. The EWS-FLI1 transcript could not be identified with reverse transcription-PCR in any of the 13 E1A-transfected cell lines analyzed. Furthermore, the EWS-FLI1 fusion protein could not be detected by Western blot analysis in E1A-transfected cell lines. These results suggest that E1A transfection does not necessarily lead to expression of the oncogenic EWS-FLI1 fusion transcript. Thus, the potential induction of this gene rearrangement by E1A gene therapy is unlikely to be clinically significant in the treatment of advanced malignant disease.
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PMID:Adenovirus 5 early region 1A does not induce expression of the ewing sarcoma fusion product EWS-FLI1 in breast and ovarian cancer cell lines. 1105 Dec 26

Molecular therapy, including gene therapy, is a promising strategy for the treatment of human disease. However, delivery of molecular therapeutics efficiently and specifically to the target tissue remains a significant challenge. A human transferrin (Tf)-targeted cationic liposome-DNA complex, Tf-lipoplex, has shown high gene transfer efficiency and efficacy with human head and neck cancer in vitro and in vivo (Xu, L., Pirollo, K.F., Tang, W.H., Rait, A., and Chang, E.H. Hum. Gene Ther. 1999;10:2941-2952). Here we explore the structure, size, formation process, and structure-function relationships of Tf-lipoplex. We have observed Tf-lipoplex to have a highly compact structure, with a relatively uniform size of 50-90 nm. This nanostructure is novel in that it resembles a virus particle with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. More importantly, compared with unliganded lipoplex, Tf-lipoplex shows enhanced stability, improved in vivo gene transfer efficiency, and long-term efficacy for systemic p53 gene therapy of human prostate cancer when used in combination with conventional radiotherapy. On the basis of our observations, we propose a multistep self-assembly process and Tf-facilitated DNA cocondensation model that may provide an explanation for the resultant small size and effectiveness of our nanostructural Tf-lipoplex system.
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PMID:Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery. 1186 Jul 13

Intensity modulated radiation therapy (IMRT), a new form of three-dimensional conformal radiation therapy (3DCRT), optimizes the concept of computer-controlled radiation deposition in tumor (target) while sparing adjacent normal structures. A retrospective review was done on the initial 185 patients with tumors in different sites including prostate cancer, head and neck cancer, pediatric tumors, adult brain tumors, and previously irradiated recurrent tumors treated with IMRT. Preliminary findings indicate that IMRT is a new clinically feasible tool in radiation oncology. Treatment-related morbidity profile was favorable. Tumor response, local control, and the ability to palliate previously irradiated patients are encouraging. Intensity modulated radiation therapy will allow dose escalation, leading to better tumor control.
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PMID:Intensity modulated radiotherapy (IMRT) decreases treatment-related morbidity and potentially enhances tumor control. 1209 38

Interleukin-12 (IL-12) is an important molecule that triggers the activation of natural killer (NK) cells and T-cells, the development of T helper type 1 (Th1) cells and the expression of antiangiogenic genes. Novel methods for IL-12 delivery include cell-based ex vivo gene therapy, viral vector-based gene therapy and DNA plasmid-based nonviral gene therapy. IL-12 electroporation gene therapy may hold some promise for tumors accessible by electrode, such as head and neck cancer, breast cancer, prostate cancer and melanoma. Codelivery of other therapeutic genes with IL-12 may enhance the therapeutic effect and reduce the level of IL-12 required for efficacy. All three approaches to IL-12 gene therapy are under clinical investigation. The preliminary results indicate that IL-12 gene therapy is safe and is not associated with any major clinical toxicity. (c) 2001 Prous Science. All rights reserved.
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PMID:IL-12-Based therapy of malignancies. 1274 34

Cancer can cause multiple impairments, activity limitations and participation restrictions. According to individual case findings and needs, rehabilitation treatment is varied. The review mainly focuses on specific problems. Because of functional deficits cancer patients suffer from persistent emotional and social distress and a reduced quality of life (QOL). QOL encompasses at least the four dimensions of physical, emotional, social and cognitive function, which may be positively influenced by physical exercise. Physical exercise also has been shown to prevent or minimise inactivity/ disuse problems and to reduce fatigue. The management of sexuality dysfunction has to begin with a thorough history taking and a consequent sexuality counselling. The goals of rehabilitation procedures under palliative care are not only to control physical pain but also to help with mental, social and spiritual pain, together with other symptoms. Rehabilitation problems in head and neck cancer, sexuality, lung cancer, prostate cancer, breast cancer and lymphedema can be improved by rehabilitation. The review mainly focuses on impairment and activity limitation. Social, psychological and vocational aspects are left aside in this review.
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PMID:Cancer rehabilitation: particularly with aspects on physical impairments. 1289 40


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