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   J Invest Dermatol 2000 Nov;115(5):893-900
   
Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma
cells and of their putative endothelial precursors.

    Simonart T, Degraef C, Andrei G, Mosselmans R, Hermans P, Van Vooren JP,
    Noel JC, Boelaert JR, Snoeck R, Heenen M
    
   Department of Dermatology, Erasme University Hospital, Brussels,
   Belgium. simonart@erasme.ulb.ac.be
   
   Iron is suspected to be involved in the induction and/or progression
   of various human tumors. More particularly, iron may be involved in
   the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular
   origin. This study was designed to investigate the effect of iron
   deprivation on Kaposi's sarcoma. The effects of iron chelators and
   iron deprivation associated with serum withdrawal were investigated on
   Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's
   sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells,
   which are the probable progenitors of Kaposi's sarcoma cells.
   Desferrioxamine and deferiprone, two chemically unrelated iron
   chelators, induced a time- and concentration-dependent inhibition of
   endothelial and Kaposi's sarcoma cell growth. The inhibition of cell
   growth was associated with a decrease in Ki-67 and in both stable and
   total proliferating cell nuclear antigen expression. Inhibition of the
   progression through the G1-phase of the cell cycle was further
   evidenced by decreased expression of cyclin D1 and of p34
   cyclin-dependent kinase 4. Terminal deoxynucleotidyl
   transferase-mediated desoxyuridinetriphosphate nick end labeling
   assay, flow cytometry with annexin-V-fluorescein and morphologic
   analysis indicated that iron chelation also induced a time- and
   concentration-dependent apoptosis. This apoptotic effect was prevented
   by the addition of exogenous iron. Induction of iron deprivation in
   the culture medium by serum withdrawal led to similar cell cycle
   effects, which, however, could only be partly reverted by the addition
   of exogenous iron. In conclusion, these results show that iron
   deprivation inhibits the growth and induces the apoptosis of Kaposi's
   sarcoma cells and of their putative endothelial precursors. This
   suggests that iron chelators may represent a potential therapeutic
   approach for the treatment of Kaposi's sarcoma.
   
   PMID: 11069629, UI: 20532598
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Subject: free radicals/breast cancer

   
   Clin Biochem 1999 Mar;32(2):131-6
   
Association between oxidative stress and changes of trace elements in patients
with breast cancer.

    Huang YL, Sheu JY, Lin TH
    
   Graduate Institute of Medicine and School of Technology for Medical
   Sciences, Kaohsiung Medical College, Taiwan, ROC.
   
   OBJECTIVES: To investigate the association between oxidative stress
   and certain trace elements in the blood of breast cancer patients.
   DESIGN AND METHODS: Malondialdehyde (MDA) was measured in serum of
   patients with breast cancer (n = 35) and controls (n = 35) by high
   performance liquid chromatography. Trace elements were determined by
   atomic absorption spectrophotometry. RESULTS: In the present study,
   significantly increased lipid peroxidation, measured as MDA, was
   demonstrated in the serum of breast cancer patients (p < 0.01). The
   concentrations of zinc and iron remained unaltered. However, the mean
   serum copper level in patients with breast cancer was significantly
   higher than the control group (p < 0.01). In addition, the mean serum
   selenium level in patients with stage III was significantly lower than
   the control group (p < 0.05). Moreover, a positive correlation was
   also observed between copper and MDA levels in the patient group but
   not in the control group. CONCLUSION: In the present study, the
   presence of an association between oxidative stress and trace elements
   was observed in patients with breast cancer. We suggest that increased
   oxidative stress in patients with breast cancer may result from
   changes in the levels of certain trace elements.
   
   Publication Types:
     * Clinical trial
     * Controlled clinical trial
       
   PMID: 10211630, UI: 99226612
     _________________________________________________________________


Subject: cancer/low iron diet

   
   Anticancer Res 1999 Jan-Feb;19(1A):445-50
   
Inhibitory effect of deferoxamine mesylate and low iron diet on the 13762NF rat
mammary adenocarcinoma.

    Wang F, Elliott RL, Head JF
    
   Mastology Research Institute, Elliott Mastology Center, Baton Rouge,
   LA 70806, USA.
   
   The iron chelator deferoxamine mesylate has been shown to inhibit the
   growth of a variety of human malignant cell lines and the rat 13762NF
   mammary adenocarcinoma cell line. In vivo studies in mice have also
   demonstrated that an iron deficiency induced by either feeding a low
   iron diet or injecting the iron chelator deferoxamine mesylate
   decreases tumor growth. In this study Fisher rats were transplanted
   with the 13762NF mammary adenocarcinoma and divided into four groups:
   normal diet, normal diet plus deferoxamine mesylate treatment, low
   iron diet and low iron diet plus deferoxamine mesylate treatment. The
   measurements of tumor size and body weight were recorded weekly. We
   found that treatment with either deferoxamine mesylate or a low iron
   diet decreased rat tumor growth, but the greatest inhibitory effect on
   tumor growth occurred when the rats were treated with deferoxamine
   mesylate injections plus fed a low iron diet. These treatments did not
   significantly inhibit the weight gain of the rats. At the end of the
   experiments measurement of serum iron proved that these treatments
   caused iron deficiency, but there was no significant treatment related
   alteration in blood hematocrit. We therefore concluded that
   deferoxamine mesylate may be a useful chemotherapeutic agent in the
   treatment of breast cancer, when used in combination with standard
   chemotherapeutic regiments or with other agents that interfere with
   iron metabolism, and further that the restricting of iron intake
   should be considered when planning chemotherapy for all cancer
   patients.
   
   PMID: 10226580, UI: 99243167
     _________________________________________________________________
   

Subject: chelator/cancer/iron

   
   Gen Pharmacol 1999 Jan;32(1):155-8
   
Dexrazoxane (ICRF-187).

    Weiss G, Loyevsky M, Gordeuk VR
    
   Department of Internal Medicine, University Hospital, Innsbruck,
   Austria. guenter.weiss@uibk.ac.at
   
   1. Dexrazoxane (ICRF-187) is the only clinically approved drug for use
   in cancer patients to prevent anthracycline mediated cardiotoxicity.
   2. The mode of action appears to be mainly due to the potential of the
   drug to remove iron from iron/anthracycline complexes and thus reduce
   free radical formation by these complexes. 3. Dexrazoxane also
   influences cell biology by its ability to inhibit topoisomerase II and
   its effects on the regulation of cellular iron homeostasis. 4.
   Although the cardioprotective effect of dexrazoxane in cancer patients
   undergoing chemotherapy with anthracyclines is well documented, the
   potential of this drug to modulate topoisomerase II activity and
   cellular iron metabolism may hold the key for future applications of
   dexrazoxane in cancer therapy, immunology, or infectious diseases.
   
   Publication Types:
     * Review
     * Review, tutorial
       
   PMID: 9888268, UI: 99103343
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Subject: breast cancer/alcohol/free radicals

   
   Free Radic Biol Med 1999 Feb;26(3-4):348-54
   
Alcohol-induced breast cancer: a proposed mechanism.

    Wright RM, McManaman JL, Repine JE
    
   Webb-Waring Antioxidant Research Institute and University of Colorado
   Health Sciences Center, Denver 80262, USA. richard.m.wright@uchsc.edu
   
   Alcohol consumption increases the risk for breast cancer in women by
   still undefined means. Alcohol metabolism is known to produce reactive
   oxygen species (ROS), and breast cancer is associated with high levels
   of hydroxyl radical (*OH) modified DNA, point mutations, single strand
   nicks, and chromosome rearrangement. Furthermore, ROS modification of
   DNA can produce the mutations and DNA damage found in breast cancer.
   Alcohol dehydrogenase (ADH) and xanthine oxidoreductase (XOR) are
   expressed and regulated in breast tissues and aldehyde oxidase (AOX)
   may be present as well. Mammary gland XOR is an efficient source of
   ROS. Recently, hepatic XOR and AOX were found to generate ROS in two
   ways from alcohol metabolism: by acetaldehyde consumption and by the
   intrinsic NADH oxidase activity of both XOR and AOX. The data obtained
   suggests that: (1) expression of ADH and XOR or AOX in breast tissue
   provides the enzymes that generate ROS; (2) metabolism of alcohol
   produces acetaldehyde and NADH that can both be substrates for XOR or
   AOX and thereby result in ROS formation; and (3) ROS generated by XOR
   or AOX can induce the carcinogenic mutations and DNA damage found in
   breast cancer. Accumulation of iron coupled with diminished
   antioxidant defenses in breast tissue with advancing age provide
   additional support for this hypothesis because both result in elevated
   ROS damage that may exacerbate the risk for ROS-induced breast cancer.
   
   Publication Types:
     * Review
     * Review, tutorial
       
   PMID: 9895226, UI: 99110517
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Subject: HEME IRON AND COLON CANCER

   
   Cancer Res 1999 Nov 15;59(22):5704-9
   
Red meat and colon cancer: the cytotoxic and hyperproliferative effects of
dietary heme.

    Sesink AL, Termont DS, Kleibeuker JH, Van der Meer R
    
   Wageningen Centre for Food Sciences, Netherlands Institute for Dairy
   Research Food Research, Ede. Sesink@nizo.nl
   
   [Medline record in process]
   
   The intake of a Western diet with a high amount of red meat is
   associated with a high risk for colon cancer. We hypothesize that
   heme, the iron carrier of red meat, is involved in diet-induced
   colonic epithelial damage, resulting in increased epithelial
   proliferation. Rats were fed purified control diets, or purified diets
   supplemented with 1.3 micromol/g of hemin (ferriheme), protoporphyrin
   IX, ferric citrate, or bilirubin (n = 8/group) for 14 days. Feces were
   collected for biochemical analyses. Fecal cytotoxicity was determined
   from the degree of lysis of erythrocytes by fecal water. Colonic
   epithelial proliferation was measured in vivo using [3H]thymidine
   incorporation into colonic mucosa. The colonic epithelial
   proliferation in heme-fed rats was significantly increased compared to
   control rats [55.2 +/- 5.8 versus 32.6 +/- 6.3 dpm/microg DNA (mean
   +/- SE); P < 0.05]. The fecal water of the heme group was highly
   cytotoxic compared to the controls (90 +/- 2% versus 2 +/- 1%; P <
   0.001), although the concentrations of cytotoxic bile acids and fatty
   acids were significantly lower. Organic iron was significantly
   increased compared to the controls (257 +/- 26 versus 80 +/- 21,
   microM; P < 0.001). Spectrophotometric analyses suggest that this
   organic iron is heme-associated. Thiobarbituric acid-reactive
   substances were greatly increased in the fecal water of heme-fed rats
   compared to the controls (177 +/- 12 versus 59 +/- 7 microM; P <
   0.05). Heme itself could not account for the increased cytotoxicity
   because the addition of heme to the fecal water of the control group,
   which was equimolar to the organic iron content of the fecal water of
   the heme group, did not influence the cytotoxicity. Hence, an
   additional heme-induced cytotoxic factor is involved, which may be
   modulated by the generation of luminal-reactive oxygen species.
   Protoporphyrin IX, ferric citrate, and bilirubin did not increase
   proliferation and cytotoxicity. In conclusion, dietary heme leads to
   the formation of an unknown, highly cytotoxic factor in the colonic
   lumen. This suggests that, in heme-fed rats, colonic mucosa is damaged
   by the intestinal contents. This results in a compensatory
   hyperproliferation of the epithelium, which supposedly increases the
   risk for colon cancer.
   
   PMID: 10582688, UI: 20047513
     _________________________________________________________________


Subject: fibroid/ferritin

   
   Chung Hua Fu Chan Ko Tsa Chih 1991 Jan;26(1):21-3, 61
   
[Evaluation of serum ferritin in female genital neoplasms].

   [Article in Chinese]
   
    Dong MY
    
   Obstetric and Gynecologic Hospital, Zhejiang Medical University,
   Hangzhou.
   
   Serum ferritin concentrations of 50 normal women and 90 patients with
   neoplasms of female genital tract were determined by radioimmunoassay.
   The mean value of serum ferritin in 23 cases of ovarian carcinoma was
   402.04 micrograms/L, significantly higher than that of normal subjects
   and patients with benign genital neoplasms. Serum ferritin levels in
   patients with endometrial carcinoma, endometrial stromal sarcoma, and
   benign genital neoplasms were significantly higher than that of the
   normal subjects. There was a positive correlation between the serum
   ferritin level and the clinical stage of ovarian carcinoma. The serum
   ferritin determination is useful in the diagnosis, differential
   diagnosis and prognosis of ovarian cancers.
   
   PMID: 1848498, UI: 91168663
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Subject: fibroid/ferritin

   
   Chung Hua Fu Chan Ko Tsa Chih 1991 Jan;26(1):21-3, 61
   
[Evaluation of serum ferritin in female genital neoplasms].

   [Article in Chinese]
   
    Dong MY
    
   Obstetric and Gynecologic Hospital, Zhejiang Medical University,
   Hangzhou.
   
   Serum ferritin concentrations of 50 normal women and 90 patients with
   neoplasms of female genital tract were determined by radioimmunoassay.
   The mean value of serum ferritin in 23 cases of ovarian carcinoma was
   402.04 micrograms/L, significantly higher than that of normal subjects
   and patients with benign genital neoplasms. Serum ferritin levels in
   patients with endometrial carcinoma, endometrial stromal sarcoma, and
   benign genital neoplasms were significantly higher than that of the
   normal subjects. There was a positive correlation between the serum
   ferritin level and the clinical stage of ovarian carcinoma. The serum
   ferritin determination is useful in the diagnosis, differential
   diagnosis and prognosis of ovarian cancers.
   
   PMID: 1848498, UI: 91168663
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Subject: iron/magnetic/cancer

   
   Med Hypotheses 2000 Feb;54(2):177-9
   
Selective treatment of neoplastic cells using ferritin-mediated electromagnetic
hyperthermia.

    Babincova M, Leszczynska D, Sourivong P, Babinec P
    
   Department of Biophysics and Chemical Physics, Comenius University,
   Bratislava, Slovakia. babincova@fmph.uniba.sk
   
   A new method of cancer treatment is proposed, based on the unique
   magnetic properties of ferritin iron core which, in alternating
   magnetic field of frequency approximately 100 kHz, is easily heated to
   temperatures sufficiently high to destroy neoplastic cells containing
   an excess of this protein, without damaging the normal cells.
   Copyright 2000 Harcourt Publishers Ltd.
   
   PMID: 10790746, UI: 20253813
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Subject: cancer/iron/diet/rectum/Uruguay

   
   Eur J Cancer Prev 1999 Dec;8(6):501-8
   
Dietary iron and cancer of the rectum: a case-control study in Uruguay.

    Deneo-Pellegrini H, De Stefani E, Boffetta P, Ronco A, Mendilaharsu M
    
   Registro Nacional de Cancer, Montevideo, Uruguay.
   
   In order to examine the relationship between dietary iron intake and
   risk of rectal cancer, a case-control study was carried out in
   Montevideo, Uruguay. In the time period 1994-1998, 216 newly diagnosed
   and microscopically verified cases of adenocarcinoma and 433 controls
   hospitalized for diseases not related with long-term changes in diet
   were enrolled in the study. Controls were frequency matched to cases
   on age, sex, residence and urban/rural status. Both series of patients
   were interviewed face-to-face in the four major hospitals in
   Montevideo by two trained social workers. Dietary iron was associated
   with significant increases in risk in men, women, and in both sexes
   together [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.9-5.3
   for the highest tertile of consumption versus the lowest one]. Since
   meat and its major macronutrients were potential confounders, iron
   intake was adjusted for these variables without major changes in the
   results. Furthermore, dietary iron and total fat combined its effects
   according to a multiplicative model (OR 3.3, 95% CI 1.8-5.8). Finally,
   an interaction between dietary iron and vitamin C was found. According
   to the results, iron displayed a significant increase in risk at low
   levels of vitamin C intake (OR 4.9, 95% CI 2.3-10.5). These results,
   together with the existing epidemiological and experimental evidence,
   suggest that dietary iron could play an important role in rectal
   carcinogenesis.
   
   PMID: 10643939, UI: 20106755
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Subject: vitamin E/tocopherol/cancer


                           Molecular Medicine

VITAMIN E SUCCINATE INDUCES APOPTOSIS IN HUMAN PROSTATE CANCER CELLS: ROLE
FOR FAS IN VITAMIN E SUCCINATE-TRIGGERED APOPTOSIS

Compare the effects of VES on human prostate carcinoma cells and normal
prostate cells in vitro.

Nutrition and Cancer 36(1):90-100, 2000
http://www.medscape.com/26577.rhtml
Read it Here



Subject: vitamin E/cancer

   
   Carcinogenesis 2000 Aug;21(8):1531-1536
   
Effects of vitamin E and selenium supplementation on esophageal
adenocarcinogenesis in a surgical model with rats.

    Chen X, Mikhail SS, Ding YW, Yang Gy, Bondoc F, Yang CS
    
   Laboratory for Cancer Research, College of Pharmacy, Rutgers
   University, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA.
   
   [Record supplied by publisher]
   
   Two well-known antioxidative nutrients, vitamin E and selenium, were
   used in this study to investigate possible inhibitory action against
   the formation of esophageal adenocarcinoma (EAC) in rats. In this
   model, carcinogenesis is believed to be driven by oxidative stress.
   Male Sprague-Dawley rats (8 weeks old) were divided into four groups
   and received esophagoduodenal anastomosis (EDA) surgery plus iron
   supplementation (12 mg/kg/week). Vitamin E and selenium were
   supplemented in the diet in the forms of alpha-tocopheryl acetate (750
   IU/kg) and sodium selenate (1.7 mg Se/kg), which were 10 times the
   regular amounts in the basic AIN93M diet. At 40 weeks after surgery,
   all the EDA groups had lower body weights than the non-operated
   control group. Iron nutrition (hemoglobin, total serum iron and
   transferrin saturation) was normal as a result of iron supplementation
   after EDA. Vitamin E supplementation maintained the normal plasma
   level of alpha-tocopherol in EDA rats, but not those of
   gamma-tocopherol and retinol. Selenium supplementation increased the
   serum and liver selenium contents of the EDA rats. Histopathological
   analysis showed that selenium supplementation increased the incidence
   of EAC and the tumor volume. The selenium level in the tumor is higher
   than that in the duodenum of the same animal.Vitamin E
   supplementation, however, inhibited carcinogenesis, especially in the
   selenium-supplemented group. We believe that vitamin E exerts its
   effect through its antioxidative properties, and a high dose of
   inorganic selenium may promote carcinogenesis by enhancing oxidative
   stress.
   
   PMID: 10910955
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Subject: bacteria/iron

   
   Clin Microbiol Rev 1996 Oct;9(4):435-447
   
Mycobacterium haemophilum: microbiology and expanding clinical and geographic
spectra of disease in humans.

    Saubolle MA, Kiehn TE, White MH, Rudinsky MF, Armstrong D
    
   Department of Pathology, Good Samaritan Regional Medical Center,
   Phoenix, Arizona 85006, USA.
   
   Reports of the association of Mycobacterium haemophilum with disease
   in humans have greatly increased. At least 64 cases have now been
   reported, with symptoms ranging from focal lesions to widespread,
   systemic disease. The organism is now known to cause primarily
   cutaneous and subcutaneous infection, septic arthritis, osteomyelitis,
   and pneumonitis in patients who are immunologically compromised and
   lymphadenitis in apparently immunocompetent children. Underlying
   conditions in the compromised patients have included AIDS; renal, bone
   marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis;
   marrow hypoplasia; and Crohn's disease. Reports have originated from
   diverse geographic areas worldwide. The epidemiology of M. haemophilum
   remains poorly defined; there appears to be a genetic diversity
   between strains isolated from different regions. The organism is
   probably present in the environment, but recovery by sampling has not
   been successful. M. haemophilum has several unique traits, including
   predilection for lower temperatures (30 to 32 degrees C) and
   requirement for iron supplementation (ferric ammonium citrate or
   hemin). These may in the past have compromised recovery in the
   laboratory. Therapy has not been well elucidated, and the outcome
   appears to be influenced by the patient's underlying
   immunosuppression. The organisms are most susceptible to
   ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely
   diagnosis and therapy require communication between clinician and the
   laboratory.
   
   Publication Types:
     * Review
     * Review, academic
       
   PMID: 8894345, UI: 97049617
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Subject: estrogen and iron

   
   Carcinogenesis 1998 Jul;19(7):1285-90
   
Enhancement of estrogen-induced renal tumorigenesis in hamsters by dietary
iron.

    Wyllie S, Liehr JG
    
   Department of Pharmacology and Toxicology, University of Texas Medical
   Branch, Galveston 77555-1031, USA.
   
   Iron participates in the generation of hydroxyl radicals by the
   iron-catalyzed Fenton reaction. Its role in estrogen-induced
   carcinogenesis has been examined in this study by investigating the
   effects of iron content of hamster diets on tumor induction by
   estradiol. The renal tumor incidence and number of tumor nodules in
   hamsters treated with estradiol plus a diet enriched with iron (384
   p.p.m. Fe as ferric citrate) for 5 months were 2- and 4-fold higher,
   respectively, than those observed in animals on an iron-poor diet plus
   estradiol (3.9 p.p.m. Fe, as ferric citrate). Tumor incidence and
   number of tumor nodules in estradiol-treated hamsters on the
   iron-deficient diet were not different from those of animals on a
   normal rodent chow. No tumors were detected in hamsters treated only
   with the low or high iron diets. Total serum iron was significantly
   increased in animals treated with the high iron diet plus estradiol
   compared with the low iron diet plus estradiol group and the high and
   low iron controls. Estrogen treatment increased non-heme iron in liver
   of both high and low iron treatment groups and in kidney of the
   hamsters on the low iron diet. It is concluded that dietary iron
   enrichment enhances the incidence and severity of estrogen-induced
   tumor induction.
   
   PMID: 9683190, UI: 98346720
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Subject: stomach cancer/iron supplements

   
   J Reprod Med 1999 Nov;44(11):986-8
   
Gastric adenocarcinoma presenting with persistent, mild gastrointestinal
symptoms in pregnancy. A case report.

    Chan YM, Ngai SW, Lao TT
    
   Department of Obstetrics and Gynecology, University of Hong Kong,
   Queen Mary Hospital, China.
   
   BACKGROUND: Mild gastrointestinal symptoms are common during pregnancy
   but can also be the only symptoms in stomach cancer until the late
   stage. Clinicians' reluctance to pursue diagnostic studies appears to
   be a major contributing factor to delayed diagnosis and poor outcome.
   We report a case of maternal death to alert clinicians to this rare
   possibility. CASE: A 36-year-old woman had persistent, mild epigastric
   discomfort, nausea, vomiting and frequent episodes of dark stools
   since the second trimester of pregnancy. These were attributed to
   peptic ulcer and an iron supplement given, without investigation.
   Gastroscopy was performed only at 32 weeks of gestation, when the
   patient had heavy hematemesis. Biopsy confirmed the diagnosis of
   poorly differentiated adenocarcinoma of the stomach. Cesarean section
   was performed after steroid therapy. Advanced stomach cancer with
   stomach perforation was found. Curative surgery was not possible. The
   patient died four weeks after delivery. CONCLUSION: Stomach cancer is
   a rare complication of pregnancy. Delay in diagnosis is commonly due
   to clinicians' reluctance to request diagnostic studies and the
   nonspecific symptoms of the disease. Early recognition and diagnosis
   are the only possibilities for a better outcome. Clinicians must be
   alert to this possibility and include this in the differential
   diagnosis of minor gastrointestinal discomfort during pregnancy.
   
   PMID: 10589414, UI: 20056854
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Subject: iron/testicular cancer

   
   Med Hypotheses 1998 Aug;51(2):129-32
   
The case for iron repletion as a promoter in testicular cancer.

    Crawford RD
    
   Department of Chemistry and Biochemistry, Loyola Marymount University,
   Los Angeles, CA 90045-8225, USA.
   
   [Medline record in process]
   
   The incidence of testicular cancer has increased considerably in this
   century. Current hypotheses (most specifically, those concerning
   environmental estrogens) show inconsistencies with this increase,
   either in terms of time course or individual exposure to proposed
   promoters. This new hypothesis, which attributes the increased
   incidence in testicular cancer to our current more iron-replete
   dietary status, is devoid of these inconsistencies. Evidence to
   support this hypothesis includes the following: (a) the iron-related
   mechanism of drugs used in the treatment of testicular cancer, (b)
   dietary associations with disease frequency, (c) the similarity of
   time course between historic increases in testicular cancer incidence
   and dietary iron availability, and (d) potential genetic associations
   with hemochromatosis. The link between incidence of the cancer and
   cyptorchidism is also addressed. The article concludes with potential
   experimental approaches to test the hypothesis.
   
   PMID: 9881819, UI: 99096146
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Subject: zinc/thyroid

   
   J Endocrinol 2001 May;169(2):417-24
   
Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines.

    Iitaka M, Kakinuma S, Fujimaki S, Oosuga I, Fujita T, Yamanaka K, Wada S,
    Katayama S
    
   Department of Internal Medicine 4, Saitama Medical School, 38
   Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
   
   Zinc at concentrations of 150, microM or higher induced necrosis as
   well as apoptosis in thyroid cancer cell lines. Necrosis was induced
   by zinc in a dose-dependent manner, whereas apoptosis did not increase
   at higher concentrations of zinc. The expression of the antiapoptotic
   protein phosphorylated Bad was markedly increased, whereas the
   expression of the proapoptotic proteins Bax and Bad decreased
   following Zn(2+) exposure. Zn(2+) induced rapid degradation of
   IkappaB, and an increase in the binding of nuclear transcription
   factor-kappaB (NF-kappaB). These observations indicate that
   antiapoptotic pathways were activated in thyroid cancer cells
   following exposure to Zn(2+). This may be a self-defence mechanism
   against apoptosis and may underlie the general resistance of thyroid
   cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic
   agent for the treatment of thyroid cancer.
   
   PMID: 11312158, UI: 21211517
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