Gene/Protein Disease Symptom Drug Enzyme Compound
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High incidences of Small Cell Carcinoma & Adenocarcinoma of the lung, Astrocytoma & Glioblastoma Multiforme of the brain and Mesothelioma of the lung were found in those who had a high accumulation of Asbestos in the eyes and upper respiratory system (nose, larynx, trachea, etc.). When measured non-invasively using the Bi-Digital O-Ring Test (BDORT), brain tumors had the highest concentration of Asbestos (0.2 approximately 2.1 mg BDORT units). Relatively high levels of Asbestos (0.2 approximately 0.6 mg BDORT units) were found in: Squamous Cell Carcinoma of the lungs & esophagus, Adenocarcinoma of the larynx & breast, myelogenic leukemia, arteries of these cancers, left ventricle of failing heart, myocardial infarction, some of the narrowed arteries, varicose veins, cataracts, balding heads, hot flashes, Alzheimer's Disease and Autism. A small, round or ellipsoidal area, with diameter of 5 mm or less, was found near the center of every cancer tissue with a higher level of Asbestos (1 approximately 3 mg), As, Zn, Cr and Se, than in the rest of the tumor; this small area may be where the cancer initiated. Among areas of intractable pain with frequent recurrence and gradual worsening, about 0.2 approximately 0.5 mg BDORT units (or higher) of Asbestos were found. The author found that in the Astrocytoma and many other cancer patients, the optimal dose of DHEA produced very significant reductions of cancer cell telomere from over 1400 ng in the brain tumors (and over 900 ng in other cancers) to close to or less than 1 yg (=10(-24) g), with circulatory improvement by reduction of TXB2. Unlike the standard, widely used treatment with DHEA 25 approximately 50 mg daily, which is an overdose; we only gave one optimal dose (1.5 approximately 12.5 mg) and the beneficial effects usually lasted anywhere between 3-6 months, unless inhibiting factors were introduced. In addition, once one optimal dose of DHEA was given, the amount of Asbestos from these tumors decreased very significantly (30 approximately 99% reduction) with marked increase in urine Asbestos. One optimal dose of special Cilantro tablet reduced more Asbestos than DHEA or (+) Qi Gong Energy Stored Paper. In addition, the application of (+) Solar Energy Stored Paper often reduces 70 approximately 99% of the Asbestos, while (+) Qi Gong Energy Stored Paper reduces 50 approximately 99% of the Asbestos.
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PMID:Asbestos as a possible major cause of malignant lung tumors (including small cell carcinoma, adenocarcinoma & mesothelioma), brain tumors (i.e. astrocytoma & glioblastoma multiforme), many other malignant tumors, intractable pain including fibromyalgia, & some cardio-vascular pathology: Safe & effective methods of reducing asbestos from normal & pathological areas. 1706 32

Novel estrogenic therapies are needed that ameliorate menopausal symptoms and have the bone-sparing effects of endogenous estrogens but do not promote breast or uterine cancer. Recent evidence suggests that selective activation of the estrogen receptor (ER)-beta subtype inhibits breast cancer cell proliferation. To establish whether ERbeta-selective ligands represent a viable approach to improve hormone therapy, we investigated whether the estrogenic activities present in an herbal extract, MF101, used to treat hot flashes, are ERbeta selective. MF101 promoted ERbeta, but not ERalpha, activation of an estrogen response element upstream of the luciferase reporter gene. MF101 also selectively regulates transcription of endogenous genes through ERbeta. The ERbeta selectivity was not due to differential binding because MF101 binds equally to ERalpha and ERbeta. Fluorescence resonance energy transfer and protease digestion studies showed that MF101 produces a different conformation in ERalpha from ERbeta when compared with the conformations produced by estradiol. The specific conformational change induced by MF101 allows ERbeta to bind to an estrogen response element and recruit coregulatory proteins that are required for gene activation. MF101 did not activate the ERalpha-regulated proliferative genes, c-myc and cyclin D1, or stimulate MCF-7 breast cancer cell proliferation or tumor formation in a mouse xenograft model. Our results demonstrate that herbal ERbeta-selective estrogens may be a safer alternative for hormone therapy than estrogens that nonselectively activate both ER subtypes.
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PMID:Selective activation of estrogen receptor-beta transcriptional pathways by an herbal extract. 1709 96

Vascular disrupting agents (VDAs), or endothelial disrupting agents, attempt to exploit the vascular endothelium that supplies rapidly dividing neoplasms. Unlike antiangiogenesis agents (e.g. the monoclonal antibody bevacizumab; and tyrosine kinase inhibitors sorafenib and sunitinib) that disrupt endothelial cell survival mechanisms and the development of a new tumor blood supply, VDAs are designed to disrupt the already established abnormal vasculature that supports tumors, by targeting their dysmorphic endothelial cells. Tumor vascular endothelium is characterized by its increased permeability, abnormal morphology, disorganized vascular networks, and variable density. VDAs induce rapid shutdown of tumor blood supply, causing subsequent tumor death from hypoxia and nutrient deprivation. The safety profile of this class of compounds is more indicative of agents that are indeed 'vascularly' active. For example, VDAs can cause: acute coronary and other thrombophlebitic syndromes; alterations in blood pressure, heart rate, and ventricular conduction; transient flush and hot flashes; neuropathy; and tumor pain. Despite these cardiovascular concerns some patients have benefited from VDAs in early clinical trials. Further drug development of VDAs must include the combination of these agents with other novel biological agents, cytotoxic chemotherapy, and radiotherapy. Close monitoring of patients receiving VDAs for any cardiovascular toxicity is imperative.
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PMID:Drug insight: vascular disrupting agents and angiogenesis--novel approaches for drug delivery. 1713 19

We describe an approach to produce an autologous therapeutic antitumor vaccine using hydroxyapatite (HA) for vaccinating cancer patients. The novel approach involved (1) the purification of part of the self-tumor antigens/ adjuvants using column chromatography with HA, (2) the employ of HA as a medium to attract antigen-presenting cells (APCs) to the vaccination site, and (3) the use of HA as a vector to present in vivo the tumor antigens and adjuvants to the patient's APCs. The vaccine was prepared using and combining HA particles, with at least 3 heat shock proteins (gp96 was one of them possibly with chaperoned proteins/peptides as shown in the slot blots) and with proteins from the cell membrane system (including Hsp70, Hsp27, and membrane proteins). The timing of HA degradation was tested in rats; the HA particles administered under the skin attracted macrophages and were degraded into smaller particles, and they were totally phagocytized within 1 week. In patients (n = 20), the vaccine was then administered weekly and showed very low toxicity, causing minor and tolerable local inflammation (erythema, papule, or local pain); only 1 patient who received a larger dose presented hot flashes, and there were no systemic manifestations of toxicity or autoimmune diseases attributed to the vaccine. Our study suggests that this therapeutic vaccine has shown some efficacy producing a positive response in certain patients. Stable disease was noted in 25% of the patients (renal carcinoma, breast carcinoma, and astrocytoma), and a partial response was noted in 15% of the patients (breast carcinoma and astrocytoma). The most encouraging results were seen in patients with recurrent disease; 4 patients in these conditions (20%) are disease free following the vaccine administration. However, we do not want to overstate the clinical efficacy in this small number of patients. The therapeutic vaccine tested in our study is working by activating the T-cell response as was shown in the comparative histological and immunohistochemical study performed in the pre- and postvaccine biopsy taken from a patient with inflammatory breast carcinoma. However, we cannot ruled out that the vaccine could also be producing an antibody(ies)-mediated response. In conclusion, this therapeutic vaccine based on HA ceramic particles and self-antigens can be safely administered and is showing some encouraging clinical results in cancer patients.
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PMID:A pilot study with a therapeutic vaccine based on hydroxyapatite ceramic particles and self-antigens in cancer patients. 1744 5

Breast cancer may recur through 15 years and beyond after diagnosis; thus, breast cancer patients require long-term follow-up after adjuvant treatment to detect recurrent disease. History taking, physical examination, and regular mammography are still the foundation of appropriate breast cancer follow-up in the adjuvant setting. Clearly, breast MRI has a role in certain high-risk patients, but in moderate-risk patients, the decision to use MRI must be based on the complexity of the clinical scenario. Other routine imaging studies (CT, positron emission tomography, and bone scans) and laboratory testing--including tumor marker assessments--in asymptomatic patients have not demonstrated an improvement in survival, quality of life, toxicity, or cost-effectiveness. Survivorship issues are also an inherent part of breast cancer follow-up; physicians should make every effort to address supportive care issues unique to breast cancer survivors including hot flashes, bone health, neuropathy, and risk-reduction strategies.
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PMID:Breast cancer follow-up in the adjuvant setting. 1836 59

Abstract Bicalutamide is a nonsteroidal antiandrogen used extensively during the start of androgen deprivation therapy with a luteinizing hormone-releasing hormone agonist to reduce occurrence of the symptoms of tumor flare in patients with metastatic prostate carcinoma. The most common adverse effects of bicalutamide are induced by its pharmacologic property of competitive androgen receptor blockade and include gynecomastia, hot flashes, fatigue, and decreased libido. Although not as common, increases in liver function test results are also seen with bicalutamide therapy. These elevations are typically transient, and patients remain asymptomatic. We describe a 59-year-old man with metastatic prostate carcinoma treated with bicalutamide as part of androgen deprivation therapy before starting chemotherapy. At baseline, his liver function test results and serum creatinine concentration were within normal limits, and an abdominal computed tomographic scan did not demonstrate liver metastasis. After 4 days of bicalutamide therapy, the patient came to the emergency department with complaints of abdominal pain, distension, and tenderness. His liver function tests were abnormal, and bicalutamide was discontinued. After 2 days of increasing liver function tests and symptoms of hepatotoxicity, the patient developed tachycardia and hypotension that was resistant to fluid resuscitation. Multiorgan damage was manifested by an alanine aminotransferase level greater than 40 times the upper limit of normal, serum creatinine concentration of 4.2 mg/dl, and troponin I level of 18 ng/ml. The patient died 8 days after bicalutamide therapy was begun secondary to multiorgan failure, most likely as a result of fulminant hepatotoxicity. The Naranjo adverse drug reaction probability scale showed a probable (score of 5) causal relationship between bicalutamide and fulminant hepatotoxicity. Fulminant hepatotoxicity is a rare but potentially fatal adverse effect of bicalutamide. Liver function tests should be monitored before and during bicalutamide therapy, even for patients who have previously completed a course of this therapy with no signs or symptoms of toxicity.
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PMID:Bicalutamide-associated fulminant hepatotoxicity. 1865 23

Testicular carcinoid tumors are rare with only limited studies. We identified 29 primary testicular carcinoid cases from 7 academic institutions. Patients ranged in age from 12 to 65 years old (mean 36). The most common presenting symptom was the sole finding of either a testicular mass or swelling seen in 15/24 cases with available information. The next most common mode of presentation was as an incidental finding seen in 6 cases. Two patients had carcinoid syndrome including diarrhea, hot flashes, and palpitations. Nineteen were pure carcinoid tumors, 3 were associated with cystic teratoma, 2 with cysts lacking epithelial lining, 4 with epidermoid cyst, and 1 with dermoid cyst. The mean size was 2.5 cm. All 29 primary carcinoids lacked associated intratubular germ cell neoplasia, unclassified type. Mitotic figures were rare in primary carcinoid tumors with only 3 cases showing more than 2 per 10 HPF; necrosis was found in only 1 case. Random scattered mild to moderate nuclear atypia was seen in 12/29 cases. Of the 28 cases found premortem, treatment included focal excision in 3 patients and radical orchiectomy in 25 patients. Follow-up, available in 24 cases, ranged from 1 to 228 months (mean 52.7 mo); of the 20 patients with testicular typical carcinoid tumors found premortem, all were alive at last follow-up without recurrences or metastases. Of the 4 patients with a primary atypical carcinoid tumor, 1 at the time of diagnosis had retroperitoneal and lung metastases who after chemotherapy underwent resection of the retroperitoneal tumor showing metastatic yolk sac tumor and embryonal carcinoma. After resection, serum AFP levels remained elevated and the patient is scheduled for salvage chemotherapy and bone marrow transplant. The other 2 patients with atypical carcinoid and follow-up had no evidence of disease at 68 and 114 months. Most primary carcinoid tumors of the testis have a benign clinical course even if associated with epidermoid/dermoid cysts, or histologically mature teratoma. However, lesions with the morphology of atypical carcinoid can occasionally exhibit metastatic spread.
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PMID:Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases. 2035 89

Soyfoods have long been recognized for their high-protein and low-saturated fat content, but over the past 20 y an impressive amount of soy-related research has evaluated the role of these foods in reducing chronic disease risk. Much of this research has been undertaken because the soybean is essentially a unique dietary source of isoflavones, a group of chemicals classified as phytoestrogens. The estrogen-like properties of isoflavones have also raised concern, however, that soyfoods might exert adverse effects in some individuals. There is intriguing animal and epidemiologic evidence indicating that modest amounts of soy consumed during childhood and/or adolescence reduces breast cancer risk. Evidence also suggests that soy reduces prostate cancer risk and inhibits prostate tumor metastasis, but additional clinical support for the chemopreventive effects of soyfoods is needed. Soy protein is modestly hypocholesterolemic and there is suggestive epidemiologic evidence that soyfoods lower risk of coronary heart disease (CHD) independent of effects on cholesterol. In clinical studies, soy favorably affects multiple CHD risk factors; however, with the exception of improved endothelial function, the data are too limited and/or inconsistent to allow definitive conclusions to be made. In regard to bone health, although recent clinical data have not supported the skeletal benefits of isoflavones, 2 large prospective epidemiologic studies found soy intake is associated with marked reductions in fracture risk. Soybean isoflavones also modestly alleviate hot flashes in menopausal women. Finally, other than allergic reactions, there is almost no credible evidence to suggest traditional soyfoods exert clinically relevant adverse effects in healthy individuals when consumed in amounts consistent with Asian intake.
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PMID:Insights gained from 20 years of soy research. 2098 Jun 39

We describe the case of a 56-year old woman with no prior psychiatric history who was diagnosed with hormone receptor positive early-stage breast cancer and who developed severe mood changes after administration of anastrozole, which resolved after discontinuation of treatment. Aromatase inhibitors (AIs) are the preferred hormonal approach for postmenopausal women with estrogen hormone sensitive breast cancer. The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen. Treatment strategies with these agents include the use of an AI as an upfront strategy for 5 years, as a sequential approach after 2-3 years of tamoxifen, or as extended use after the classical 5 years of tamoxifen. The side effects of AIs, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen. However, the use of AIs have been associated with loss of bone density, arthralgia, myalgia, a negative effect on lipid metabolism, and cardiovascular risk (Tomao et al., 2011). Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy.
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PMID:Aromatase inhibitors and mood disturbances. 2267

Vertigo is one of the usual menopausal symptoms. We have often examined some women under the complaint of vertigo related with the menopause. We diagnosed each disease based on neuro-otological examinations and investigated the characteristics of menopausal-associated vertigo. We studied 413 women aged 40-59 years old who complained of vertigo. There were 73 women with menopause symptoms (14 women introduced from the gynecologist in our medical center, 18 women had undergone treatment at another female clinic, and 41 women visited an otorhinolaryngologist first) compared with 340 women without menopause symptoms. In the menopause group, 41 (56.2%) cases were diagnosed as having benign paroxysmal positional vertigo (BPPV), 13 (17.8%) cases had Meniere's disease, sudden deafness with vertigo accounted 2 cases, one was an acoustic tumor, and so on. The percentage of patients with BPPV was almost same ratio between the menopause group (56.2%) and the non-menopause group (52.9%). The percentage of patients with Meniere's disease was higher markedly in the menopausal group (17.8%). than the non-menopause group (9.7%). Menopausal symptoms are caused not only by hot flashes related to a lack of estrogen but also by psychological factors. The onset of Meniere's disease can also be influenced by psychological factors. As for the diagnosis of Meniere's disease, we supposed the reason for the higher percentage in the menopausal group was its relationship with psychological factors. We could diagnose and treat some menopausal women with vertigo. We believe that joint consultation with a gynecologist and otorhinolaryngologist would be necessary to ensure an optimum quality of life for such patients.
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PMID:[Clinical evaluation of vertigo in menopausal women]. 2268 64


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