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)

Mitoxantrone is an anthraquinone antineoplastic agent with structural similarities to doxorubicin. It has a mechanism of action similar to the anthracyclines. Its primary elimination route is hepatic metabolism (only seven percent renal excretion) and it has a terminal half-life of approximately 40 hours. Mitoxantrone has significant activity in the treatment of metastatic breast cancer, acute leukemias, and non-Hodgkin's lymphoma. Some activity is reported in head and neck cancer, Hodgkin's, myeloma, bladder cancer, prostate cancer, non-small-cell lung cancer, and liver cancer. There is a suggestion of incomplete cross-resistance between mitoxantrone and the anthracyclines in certain neoplasms. Some activity is reported with mitoxantrone in patients refractory to the anthracyclines in breast cancer, acute leukemias, and non-Hodgkin's lymphomas. The usual doses used in solid tumors and in lymphomas are mitoxantrone 12-14 mg/m2 iv q3-4wk and in leukemias is mitoxantrone 12 mg/m2/d X 5 d iv for initial induction.
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PMID:Mitoxantrone. 351 24

The first clinical case of a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was presented by Schwartz et al. in 1957 (Am J Med 1957; 23: 529-42), describing two patients with lung cancer who developed hyponatraemia associated with continued urinary sodium loss. They postulated that the tumours led to the inappropriate release of antidiuretic hormone (ADH), later discovered to consist of arginine-vasopressin (AVP). This suggestion was later confirmed in several studies. The clinical description of the syndrome has changed little since the original observation, and the cardinal findings of SIADH are as follows: (i) hyponatraemia with corresponding hypo-osmolality of the serum and extracellular fluid, (ii) continued renal excretion of sodium. (iii) absence of clinical evidence of fluid volume depletion, (iv) osmolality of the urine greater than that appropriate for the concomitant osmolality of the plasma, i.e. urine less than maximal diluted, and (v) normal function of kidneys, suprarenal glands and thyroid glands. Measurement of AVP in plasma is not a part of the definition of SIADH. SIADH may be caused by a variety of malignant tumours, but may also be caused by various other conditions, such as disorders involving the central nervous system, intrathoratic disorders such as infections, positive pressure ventilation and conditions with decrease in left atrial pressure. Also, a large number of pharmaceutical agents have been shown to produce SIADH, including a number of cytotoxic drugs such as vincristine, vinblastine, cisplatin, cyclophosphamide, and melphalan. A broad spectrum of malignant tumours has been reported to cause SIADH; however, most of these observations have been in case reports including very few patients. This includes a number of primary brain tumours, haematologic malignancies, intrathoracic non-pulmonary cancers, skin tumours, gastrointestinal cancers, gynaecological cancer, breast-and prostatic cancer, and sarcomas. Larger series of patients have revealed that SIADH occurs in 3% of patients with head and neck cancer (47 cases out of 1696 patients), in 0.7% of patients with non-small-cell lung cancer (three cases out of 427 patients), and in 15% of cases of small-cell lung cancer (214 cases out of 1473 patients). The optimal therapy for SIADH is to treat the underlying malignant disease. If this is not possible, or if the disease has become refractory, other treatment methods are available such as water restriction, demeclocycline therapy, or, in severe cases, infusion of hypertonic saline together with furosemide during careful monitoring.
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PMID:Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease. 762 92

Serum tissue polypeptide antigen (TPA) was measured using a newly developed Prolifigen TPA-M "Daiichi" kit in 1,236 healthy subjects, 2,867 patients with malignant tumors, and 901 with benign diseases. Because 94.0% of healthy subjects had serum TPA under 70 U/l, the cut-off value was set at 70 U/l. Serum TPA was elevated in more than 50% of patients with head and neck cancer, lung cancer, liver cancer, gallbladder or bile duct cancer, pancreatic cancer, colorectal cancer, ovarian cancer, and prostate cancer. The overall positive rate in malignant tumors was 55.5%. Serum TPA was higher in advanced cancer than in earlier stage cancer, and decreased after the resection of the tumor. The false positive rate in benign diseases was 31.3%. ROC analysis revealed the usefulness of TPA as a tumor marker in many cancers. The correlation coefficient between TPA and CYFRA 21-1, and between TPA and TPSA, was 0.747 and 0.694, respectively. In conclusion, measurement of serum TPA using the new kit is useful in the management of patients with various malignant tumors.
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PMID:[Measurement of serum tissue polypeptide antigen (TPA) in patients with malignant tumor using prolifigen TPA-M "Daiichi" kit]. 864 25

To arrive at a reasonable estimate of the total need for radiotherapy, the various descriptions of population trends and measures of cancer trends must be studied concurrently. Incidence and mortality are well documented by official statistics. All prognoses are based on these measures, the official population statistics, and the 1989 population prognosis from Statistics Sweden. Incidence, mortality, and prevalence may be considered either individually or together as indirect measures of the need for radiotherapy at different stages for different types of cancer. Incidence, ie, the number of cases of disease onset during a given period, shows the indirect need for curative radiotherapy, eg, for breast cancer, laryngeal cancer, gynecological tumor types, and head and neck cancer. The projected average annual mean increase in total incidence is 1.0%. Mortality may be used as an indirect measure of the need for palliative treatment for recurring cancer, eg, for bone metastases, prostate cancer, lung cancer, or breast cancer. The mean increase is estimated at 0.9% per year. Likewise, prevalence can be an indirect measure of the need for palliative treatment for cancer diseases of a chronic nature, eg, prostate cancer and multiple myeloma. The total mean increase per year has been estimated at 2.0%. The total need for radiotherapy in the future should be viewed against the background of all these descriptive measures. Assessment must also consider numerous other factors that directly influence need. A change in the indications for treatment can quickly increase the need for radiotherapy, eg, the benefits of radiotherapy for noninvasive breast cancer are currently being studied. Even a change in the indications for surgical intervention for small tumors in the breast influence the need for primary curative radiotherapy in this large group of patients. Likewise, a shift in staging the primary diagnosis, eg, in head and neck cancer, and changes in fractionation (hyperfractionation) may substantially influence need. This is addressed further in another section of the report. The largest single group of cancer patients who receive radiotherapy are those with bone metastases (25% of the total). The size of this group, and thereby the potential unsatisfied need, is largely unknown since no statistics show the prevalence of metastases in the population. This group is comprised mainly of patients that were primarily diagnosed with prostate cancer, breast cancer, and lung cancer. Concerning lung cancer, incidence trends probably provide the best measure of changes in the number of bone metastases over time. The annual increase in incidence has been estimated at 1.5%. As for breast cancer and prostate cancer, mortality trends provide more information about trends in the number of bone metastases. Both types of cancer increased by 1.9% per year. Chapter 6 presents the types of cancer for which radiotherapy is usually given. The projected trends show that each of these cancer diagnoses, except lung cancer in men and cervical cancer in women, are expected to increase in number until the year 2010. Prevalence is expected to increase even more, particularly cancer in the rectum, breast, and prostate. Also, the number of cases of non-Hodgkin's lymphoma is expected to nearly double by 2010.
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PMID:Cancer trends in Sweden until 2010. 915 84

A prospective survey was conducted of patients who began radiotherapy in Sweden during 12 weeks in the autumn of 1992. All hospitals that provided radiotherapy participated. The goal was to study the most common diagnoses, corresponding to approximately 80% of the patients. A special analysis involving all patients who started radiotherapy in 1992 at Sweden's largest unit, Radiumhemmet in Stockholm, revealed that the goal had been achieved. Overall, the assessment showed the data to be representative and of good quality. The analysis included 2988 patients, of whom 2776 received external radiotherapy alone, 63 received both external radiotherapy and brachytherapy, and the remaining 149 received brachytherapy alone. As expected, the two most common diagnoses were breast cancer and prostate cancer. To evaluate the total number of patients receiving radiotherapy in Sweden in 1992, the results of the study were related to the results of the economic assessment from 1991 described in Chapter 8. The assessment shows that approximately 13000 patients began radiotherapy in Sweden in 1992, ie, almost one third of cancer patients receive radiotherapy at some time during the course of their disease. The mean age of radiotherapy patients was 64 years, and 55% of all patients were women. Half of the patients received curative treatment, and the other half palliative treatment. The proportion of curative treatments varied considerably among the departments, from 23% to 86%. The proportion was 39% at county departments, compared to 52% at regional departments, and 76% at the gynecologic oncology departments. Palliative treatment was usually provided by less complicated methods, using fewer fractions and fewer fields. The proportion of curative fractions was 68%, and the proportion of curative fields was 72%. The proportion of curative treatments also varied greatly among different diagnostic groups, from 82% for head and neck cancer to 17% for lung and prostate cancer. Of patients receiving primary treatment, one third received radiotherapy alone and the remainder received a combination of radiotherapy and other treatment, usually surgery. Thirty-three percent of the patients were treated in accordance with clinical protocols or studies, with a somewhat higher proportion of these patients at the gynecologic oncology departments. The figures varied between 82% for gastrointestinal cancer and 11% for prostate cancer. Curative treatment was delivered, on average, using 23 fractions, 2.6 fields, and 49 Gy. The highest dosage, most fractions, and most fields were delivered for prostate cancer and head and neck cancer. The lowest doses were given for malignant lymphoma. Corresponding figures for palliative treatment were 11 fractions, 2.0 fields and 30 Gy. Of patients receiving palliative therapy, 60% were treated for bone metastases. These patients were treated with 8 fractions, 1.7 fields, and 27 Gy. With regard to curative and palliative treatment alike, there was a tendency for regional departments to give more fractions and higher doses than the county departments. No differences in sex or age appeared regarding the number of fractions, the number of fields, and the dose, except in patients over age 85 years where lower figures reflected a higher proportion of palliative treatments. With one exception only, patients with gynecologic cancer were the ones who received brachytherapy. Seventy percent of the patients had cancer in the body of the uterus. They received an average of four treatments, three for those who also received external radiotherapy. The number of brachytherapy treatments varied widely by department. This can be explained by two different therapeutic traditions: one tradition uses agents with low radiation intensity per time unit, resulting in fewer and longer treatments, and the second tradition involves agents with high radiation intensity per time unit, resulting in more, although shorter, treatments.
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PMID:A prospective survey of radiotherapy in Sweden. 915 85

Brachytherapy is a radiotherapeutic technique that allows the physician to implant radioactive isotopes into a body cavity or directly into tissue. Different radioisotopes have unique characteristics that the brachytherapist may utilize for a particular situation. The use of brachytherapy is part of standard radiation oncology practice in gynecological and head and neck cancer management. The prostate is approachable for interstitial implantation due to its close proximity to the perineum. Over 20 years ago, primitive methods of brachytherapy were utilized in the treatment of prostate cancer. However, poor results due to inconsistency in achieving adequate coverage of the entire prostate and poor patient selection caused this treatment modality to fall out of favor. Technological advances over the last decade have restored attention to brachytherapy for prostate cancer. Particularly important has been the development of transrectal ultrasound, new radioisotopes such as palladium-103, computer tomography, computerized dosimetry systems, and earlier diagnosis. Modern interstitial implantation utilizing transperineal template and transrectal ultrasound guidance has resulted in improved consistency in radiation dose delivery to the entire prostate. Early results are encouraging in terms of the relatively low morbidity of the procedure, improved local control rates, and biochemical progression free survival. This has resulted in an outpatient treatment that has high patient acceptance.
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PMID:Interstitial implantation techniques in prostate cancer. 929 Jun 96

The records of 1,371 patients with small cell carcinoma of the lung (SCLC) treated between 1983 and 1994, were reviewed for the occurrence of second primary malignancies (SPM). One was excluded for analysis because of insufficient data. Eight synchronous SPM (SSPM) and 8 metachronous SPM (MSPM) were identified, SSPM included non-small cell lung cancer in 6 patients, 1 head and neck cancer and 1 oesophageal cancer. Median survival after the diagnosis of SSPM was 6 months. The MSPM were detected between 1 and 6 years after the diagnosis of SCLC. MSPM included lung cancer (3 patients), gastrointestinal malignancies (2 patients), 1 hematologic malignancy, 1 prostatic cancer and 1 head and neck cancer. The median survival time after the diagnosis of MSPM was 4 months. Occurrence of SPM is a singular pattern of patients with SCLC. Tobacco consumption, genetic factors and carcinogenic effects of multimodality treatment are supposed mechanisms to explain SPM.
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PMID:[Second primary cancers after small-cell lung cancer]. 933 85

Following the demonstration of efficacy, tolerability and quality-of-life benefits of raltitrexed ('Tomudex'), principally in advanced colorectal but also in other cancers, an extensive evaluation of combination therapy with other agents in patients with colorectal and other tumour types is being undertaken. This work has been prompted by preclinical observations of enhanced activity of raltitrexed when coadministered with other cytotoxic agents or radiotherapy and by preliminary results showing the activity of raltitrexed in patients with cancers other than colorectal. Raltitrexed is currently being investigated as monotherapy in phase I and II cancer studies, including head and neck cancer, hormone-resistant prostate cancer, paediatric and adult leukaemias and solid tumours, and soft tissue sarcoma. In addition, phase I clinical trials are evaluating the drug in combination with taxanes (paclitaxel) in solid tumours, anthracyclines (doxorubicin) in gastric carcinoma, topoisomerase I inhibitors (CPT-11) and 5-fluorouracil (both infusion and bolus regimens) in advanced colorectal cancer, platinum compounds (oxaliplatin and cisplatin) in a variety of tumours and radiotherapy in rectal cancer. Preliminary reports indicate good tolerability and acceptability of the combinations being investigated, with no dose-limiting toxicity being reported to date, and some early indications of efficacy.
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PMID:New developments in cancer treatment with the novel thymidylate synthase inhibitor raltitrexed ('Tomudex'). 957 53

Mitoguazone (methylglyoxal bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic polycarbonyl derivative with activity in patients with Hodgkin's and non-Hodgkin's lymphoma, head and neck cancer, prostate cancer, and esophageal cancer. Mitoguazone has also recently been documented to have activity in patients with AIDS-related lymphoma. Among anticancer drugs, mitoguazone has a unique mechanism of action via interference with the polyamine biosynthetic pathway. Polyamines stabilize DNA structure by non-covalent cross-bridging between phosphate groups on opposite strands. In addition, mitoguazone causes uncoupling of oxidative phosphorylation. In this study, the ability of mitoguazone to induce apoptosis by inhibiting the polyamine pathway was assessed in three Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3). Additional evaluations were performed in two human breast cancer cell lines (MCF7 with wild-type p53 and VM4K with mutated p53) to determine whether the p53 tumor suppressor gene was required for efficient apoptosis induction. The present study demonstrated that mitoguazone induces apoptosis in all the different human cancer cell lines tested in a concentration- and time-dependent way, and triggers a p53-independent programmed cell death in the human breast cancer MCF7 cell line.
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PMID:Mitoguazone induces apoptosis via a p53-independent mechanism. 977 8

The human multidrug resistance protein (MRP) gene encodes a membrane protein involved in the ATP-dependent transport of hydrophobic compounds. We previously isolated a canalicular multispecific organic anion transporter, cMOAT1/MRP2, that belongs to the ATP binding cassette (ABC) superfamily, which is specifically expressed in liver, and cMOAT1/MRP2 is responsible for the defects in hyperbilirubinemia II/Dubin-Johnson syndrome. In this study, we isolated a new cDNA of the ABC superfamily designated cMOAT2/MRP3 that is homologous to human MRP1 and cMOAT1/MRP2: cMOAT2/MRP3 is 56% identical to MRP1 and 45% identical to cMOAT1/MRP2, respectively. Fluorescence in situ hybridization demonstrated the chromosomal locus of this gene on chromosome 17q22. The human cMOAT2 cDNA hybridized to a 6.5-kb mRNA that was mainly expressed in liver and to a lesser extent in colon, small intestine, and prostate. The cMOAT2/MRP3 gene was not overexpressed in cisplatin-resistant cell lines with increased ATP-dependent transport of cisplatin over their parental counterparts derived from human head and neck cancer and human prostatic cancer cell lines. The human cMOAT2/MRP3, a novel member of the ABC superfamily, may function as a membrane transporter in liver, colon, and prostate.
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PMID:Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. 981 53


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