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1. Sa ki N, Tamaki K, Murai H, Kubota M, Yamaura A, Uchida D, Noguchi Y, Nakamura S, Tatsuno I, Wada K, Minagawa M, Yasuda T: Long-term outcome of endocrine function in patients with neurohypophyseal germinomas. Endocr J; 2000 Feb;47(1):83-9
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  • Since neurohypophyseal germinomas occur at the pituitary and hypothalamic axis in children and adolescents, the endocrinopathy is one of the common and critical QOL determinants.
  • We carried out a retrospective study on the outcome of endocrine function in patients with neurohypophyseal germinoma, in order to improve or preserve pituitary function after treatment.
  • DI was noted in 12 patients in pretreatment and 16 in posttreatment regardless of tumor size.
  • Patients with large tumor compressing chiasm or hypothalamus needed hormonal replacement such as gonadal or gonadotropic and thyroid hormones more frequently (<0.01) than those with small one.
  • In addition, two patients with a small tumor at the pituitary stalk and the 3rd ventricle floor showed the improvement of secretion pattern in gonadotropins and ACTH after chemotherapy, although they later needed radiation therapy to control the tumor.
  • Based on our study and review of literature, the endocrinological studies before and after treatment demonstrated that pituitary dysfunction present before treatment persisted or worsened even after tumor remission, except for patients with small and localized ones.
  • Chemotherapy alone seems to be insufficient to obtain complete response (CR).
  • To avoid radiation related pituitary injury, combination of 24 Gy or less dosage of radiation and appropriate chemotherapy is essential.
  • The earlier diagnosis by repeatedly using neuroimaging and serum and CSF tumor markers and earlier initiation of treatment, before irreversible pituitary-hypothalamic damage occurs, contributes to improvement of the outcome of pituitary functions in patients with neurohypophyseal germinomas.
  • [MeSH-major] Endocrine Glands / physiopathology. Germinoma / physiopathology. Pituitary Gland, Posterior. Pituitary Neoplasms / physiopathology
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Agents / therapeutic use. Child. Cisplatin / therapeutic use. Combined Modality Therapy. Female. Gonadotropin-Releasing Hormone. Growth Hormone / therapeutic use. Hormones / therapeutic use. Humans. Insulin. Male. Pituitary Gland, Anterior. Retrospective Studies. Thyrotropin-Releasing Hormone

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  • (PMID = 10811297.001).
  • [ISSN] 0918-8959
  • [Journal-full-title] Endocrine journal
  • [ISO-abbreviation] Endocr. J.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] JAPAN
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Hormones; 0 / Insulin; 33515-09-2 / Gonadotropin-Releasing Hormone; 5Y5F15120W / Thyrotropin-Releasing Hormone; 9002-72-6 / Growth Hormone; Q20Q21Q62J / Cisplatin
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2. Franchi S, Sacerdote P, Moretti S, Gerra G, Leccese V, Tallone MV, Panerai AE, Somaini L: The effects of alcoholism pharmacotherapy on immune responses in alcohol-dependent patients. Int J Immunopathol Pharmacol; 2010 Jul-Sep;23(3):847-55
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  • [Title] The effects of alcoholism pharmacotherapy on immune responses in alcohol-dependent patients.
  • The use of pharmacotherapy is increasingly applied to enhance the percentage of success in maintaining alcoholic patients in remission.
  • Disulfiram, naltrexone and gamma hydroxybutiric acid are the drugs used for this purpose in Italian Addiction Services.
  • In this study we analyze the effect of pharmacotherapy of alcohol dependence on immune responses in alcoholics.
  • Group B consisted of 10 patients abstinent from alcohol in treatment only with group therapy.
  • The level of activity of the hypothalamus pituitary adrenal axis was assessed.
  • Both ACTH and cortisol levels in plasma were elevated in alcoholic patients with no treatment.
  • In patients undergoing pharmacological treatment, none of the immune parameters were different from those observed in healthy controls, independently of the type of drug administered.
  • These data indicate that pharmacotherapy more than group therapy treatment is able to ameliorate the immune system functioning in alcoholic patients.
  • [MeSH-major] Alcohol Deterrents / therapeutic use. Alcoholism / drug therapy. Alcoholism / immunology
  • [MeSH-minor] Adrenocorticotropic Hormone / blood. Adult. Cell Proliferation / drug effects. Cytokines / biosynthesis. Diagnostic and Statistical Manual of Mental Disorders. Female. Humans. Hydrocortisone / blood. Hypothalamo-Hypophyseal System / metabolism. Immunity, Cellular / drug effects. Interleukin-1 / biosynthesis. Lymphocytes / drug effects. Lymphocytes / immunology. Male. Middle Aged. Socioeconomic Factors. Th1 Cells / drug effects. Th1 Cells / metabolism. Th2 Cells / drug effects. Th2 Cells / metabolism. Tumor Necrosis Factor-alpha / biosynthesis

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  • (PMID = 20943056.001).
  • [ISSN] 0394-6320
  • [Journal-full-title] International journal of immunopathology and pharmacology
  • [ISO-abbreviation] Int J Immunopathol Pharmacol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Alcohol Deterrents; 0 / Cytokines; 0 / Interleukin-1; 0 / Tumor Necrosis Factor-alpha; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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3. Schmiegelow M, Feldt-Rasmussen U, Rasmussen AK, Poulsen HS, Müller J: A population-based study of thyroid function after radiotherapy and chemotherapy for a childhood brain tumor. J Clin Endocrinol Metab; 2003 Jan;88(1):136-40
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  • [Title] A population-based study of thyroid function after radiotherapy and chemotherapy for a childhood brain tumor.
  • The effect of craniospinal irradiation (CSI) vs. cranial irradiation (CIR) only with or without chemotherapy (CT) on the hypothalamus/pituitary (HP) thyroid axis was assessed in a population-based study of patients treated for a childhood brain tumor not directly involving the HP axis.
  • The biological effective dose (BED) of radiotherapy, determined for the HP region and spine and expressed in grays (Gy) as BED, gives a means of expressing the biological effects of different dosage schedules in a uniform way.
  • The median age at time of radiotherapy was 8.4 yr (range, 0.8-14.9).
  • There was no significant difference between CSI and the CIR only patients with respect to median BED to the HP region.
  • There was a significant relation between basal TSH and time of follow-up (r(s) = -0.39; P = 0.001).
  • In contrast, age at radiotherapy, BED to the HP region and spine, and whether the patient had been treated with CT were not included in the model.
  • In conclusion, these data suggest that both CSI and CIR for childhood brain tumor may affect the HP-thyroid axis, resulting in hypothyroidism.
  • We recommend prolonged surveillance of pituitary-thyroid function in long-term survivors of childhood brain tumor and institution of thyroid hormone replacement if the levels of TSH and free T4 are above and below the normal range, respectively, to ensure normal growth and metabolism.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Brain Neoplasms / drug therapy. Brain Neoplasms / radiotherapy. Cranial Irradiation / adverse effects. Thyroid Gland / physiopathology


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4. Mezo G, Manea M, Szabí I, Vincze B, Kovács M: New derivatives of GnRH as potential anticancer therapeutic agents. Curr Med Chem; 2008;15(23):2366-79
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  • [Title] New derivatives of GnRH as potential anticancer therapeutic agents.
  • GnRH (gonadotropin-releasing hormone), a decapeptide produced by the hypothalamus, plays an important role in the reproduction by regulating the pituitary-gonadal axis.
  • Continuous high doses of GnRH or its superactive agonists result in desensitization of the pituitary gonadotropes and a suppression of sex steroid production by the gonads (chemical castration).
  • Based on these effects, the treatment with GnRH agonists has become a widely used hormonal therapy of the sex-steroid dependent tumors.
  • It was also demonstrated that most tumor cells contain GnRH receptors, and the direct antiproliferative effect of GnRH analogs on cancer cells might be mediated by these receptors.
  • However, its endocrine effect is insignificant in mammals. lGnRH-III dimers and conjugates were prepared and were shown to have increased antiproliferative effects on various cancer cells, while their hormonal activity was lower than that of the native hormone. lGnRH-III was applied as targeting moiety to deliver anticancer agents to tumor cells.
  • Research data concerning lGnRH-III and its analogs represent a new outlook for research trends of the application of GnRH compounds in cancer chemotherapy.
  • [MeSH-major] Antineoplastic Agents / chemistry. Antineoplastic Agents / therapeutic use. Gonadotropin-Releasing Hormone / analogs & derivatives. Gonadotropin-Releasing Hormone / therapeutic use. Neoplasms / drug therapy
  • [MeSH-minor] Animals. Humans. Photosensitizing Agents / chemistry. Photosensitizing Agents / therapeutic use. Receptors, LHRH / metabolism. Signal Transduction / drug effects

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  • (PMID = 18855666.001).
  • [ISSN] 0929-8673
  • [Journal-full-title] Current medicinal chemistry
  • [ISO-abbreviation] Curr. Med. Chem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Photosensitizing Agents; 0 / Receptors, LHRH; 33515-09-2 / Gonadotropin-Releasing Hormone
  • [Number-of-references] 131
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5. Yock T, Schneider R, Friedmann A, Adams J, Fullerton B, Tarbell N: Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons. Int J Radiat Oncol Biol Phys; 2005 Nov 15;63(4):1161-8
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  • BACKGROUND: Over 85% of pediatric orbital rhabdomyosarcoma (RMS) are cured with combined chemotherapy and radiation.
  • Proton radiation can provide excellent tumor dose distributions while sparing normal tissues better than photon irradiation.
  • The percent of normal tissue spared by using protons was calculated.
  • RESULTS: Seven children were treated for orbital rhabdomyosarcoma with proton irradiation and standard chemotherapy.
  • There was an advantage in limiting the dose to the brain, pituitary, hypothalamus, temporal lobes, and ipsilateral and contralateral orbital structures.
  • Tumor size and location affect the degree of sparing of normal structures.
  • CONCLUSIONS: Fractionated proton radiotherapy is superior to 3D conformal photon radiation in the treatment of orbital RMS.
  • Proton therapy maintains excellent tumor coverage while reducing the radiation dose to adjacent normal structures.
  • Proton radiation therapy minimizes long-term side effects.
  • [MeSH-major] Orbital Neoplasms / radiotherapy. Photons / therapeutic use. Protons / therapeutic use. Rhabdomyosarcoma / radiotherapy

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  • (PMID = 15950401.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / 5 PO1 CA 21239-26
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Protons
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6. Valera ET, Lucio-Eterovic AK, Neder L, Scrideli CA, Machado HR, Carlotti-Junior CG, Queiroz RG, Motta FJ, Tone LG: Quantitative PCR analysis of the expression profile of genes related to multiple drug resistance in tumors of the central nervous system. J Neurooncol; 2007 Oct;85(1):1-10
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  • [Title] Quantitative PCR analysis of the expression profile of genes related to multiple drug resistance in tumors of the central nervous system.
  • OBJECTIVES: To evaluate and compare the profile of expression of genes related to drug resistance in brain tumors and to analyze the impact of the increased expression of these genes on overall survival.
  • METHODS: Eighty microdissected brain tumor samples from 79 patients were analyzed by RQ-PCR for the genes MDR1, MRP1, MRP3, LRP and BCRP.
  • The profile of gene expression of primary pilocytic astrocytomas of the hypothalamus and of the other locations was similar.
  • CONCLUSIONS: Drug resistance genes do not explain the higher sensitivity of gliomas of the hypothalamus/pituitary/optic pathways to chemotherapy.
  • High MDR1, MRP3 and LRP levels may be implicated in the primary resistance of pilocytic astrocytomas to chemotherapy.
  • [MeSH-major] Central Nervous System Neoplasms / genetics. Drug Resistance, Multiple / genetics. Drug Resistance, Neoplasm / genetics. Gene Expression Regulation, Neoplastic / genetics. Gene Expression Regulation, Neoplastic / physiology. Reverse Transcriptase Polymerase Chain Reaction / methods
  • [MeSH-minor] Adolescent. Adult. Aged. Brain Neoplasms / drug therapy. Brain Neoplasms / genetics. Brain Neoplasms / mortality. Calibration. Child. Child, Preschool. DNA Primers. Female. Gene Expression Profiling. Glioma / drug therapy. Glioma / genetics. Glioma / mortality. Humans. Immunohistochemistry. Infant. Male. Medulloblastoma / drug therapy. Medulloblastoma / genetics. Medulloblastoma / mortality. Middle Aged. RNA, Neoplasm / biosynthesis. RNA, Neoplasm / genetics. Survival Analysis

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  • (PMID = 17429576.001).
  • [ISSN] 0167-594X
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA Primers; 0 / RNA, Neoplasm
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7. Sklar CA: Childhood brain tumors. J Pediatr Endocrinol Metab; 2002 May;15 Suppl 2:669-73
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  • These tumors are the second most common type of childhood cancer and the most frequent of the solid tumors.
  • CNS tumors are diverse, representing many histological types and arising in a variety of anatomic sites.
  • The current 5-year survival rate for all pediatric CNS tumors is 67%, but rates differ considerably among tumor types.
  • Treatment modalities also differ according to histological type.
  • Currently, about 25% of patients are treated with surgery alone, 40% undergo surgery plus radiation, and 30% are treated with surgery, radiation, and chemotherapy.
  • Five-year survivors of brain tumors are 13 times more likely to die than healthy age- and sex-matched peers.
  • [MeSH-minor] Child. Humans. Hypothalamus / pathology. Pituitary Neoplasms / pathology. Treatment Outcome

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  • (PMID = 12092679.001).
  • [ISSN] 0334-018X
  • [Journal-full-title] Journal of pediatric endocrinology & metabolism : JPEM
  • [ISO-abbreviation] J. Pediatr. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 20
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8. Paulino AC, Simon JH, Zhen W, Wen BC: Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys; 2000 Dec 1;48(5):1489-95
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  • PURPOSE: To examine the long-term effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma.
  • There were 11 males and 6 females, with a median age of 5.7 years (range 2.2-11.6) at the time of radiotherapy.
  • Tumor location was orbit in 6 patients, infratemporal fossa in 4, paranasal sinuses in 2, and supraglottic larynx in 2; the nasopharynx, pterygopalatine fossa, and parotid gland were sites for the remaining children.
  • The Intergroup Rhabdomyosarcoma Study (IRS) Group was I in 2, II in 3, and III in 11 children; 1 patient had a recurrent tumor after surgery alone.
  • Radiotherapy volume was the primary tumor or tumor bed in 13, tumor and whole brain in 3, and tumor and craniospinal axis in 1.
  • All but 1 were treated with 150-200-cGy fractions; 1 patient received 250-cGy fractions for a tumor in the larynx.
  • Chemotherapy was vincristine (V), actinomycin-D (A), and cyclophosphamide (C) in 10 patients, VAC + adriamycin in 2, VA in 1, VA + ifosfamide in 1, VC + adriamycin in 1, and none in 2.
  • One patient had salvage chemotherapy consisting of cisplatin and etoposide.
  • Median follow-up time was 20 years (range 7.5-33).
  • RESULTS: Late effects of treatment were seen in all patients and included facial growth retardation in 11, neuroendocrine dysfunction in 9, visual/orbital problems in 9, dental abnormalities in 7, hearing loss in 6, and hypothyroidism in 3.
  • While neuroendocrine, thyroid, dental, and cognitive sequelae were primarily attributed to radiotherapy, hearing loss was thought to be a direct result of tumor destruction and, in 1 case, cisplatin chemotherapy.
  • CONCLUSION: Late effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma are frequent.
  • Late toxicity of treatment beyond 10 years is not as frequent as those occurring within 10 years of therapy.
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Child, Preschool. Cochlea / drug effects. Cochlea / radiation effects. Cognition / radiation effects. Combined Modality Therapy. Cranial Irradiation / adverse effects. Dentition. Educational Status. Facial Asymmetry / etiology. Female. Follow-Up Studies. Growth / radiation effects. Growth Hormone / deficiency. Growth Hormone / radiation effects. Humans. Hypothalamus / radiation effects. Male. Orbital Neoplasms / radiotherapy. Pituitary Gland / radiation effects. Radiotherapy Dosage. Time Factors. Vision Disorders / etiology

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  • (PMID = 11121653.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 9002-72-6 / Growth Hormone
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9. Saran FH, Baumert BG, Khoo VS, Adams EJ, Garré ML, Warrington AP, Brada M: Stereotactically guided conformal radiotherapy for progressive low-grade gliomas of childhood. Int J Radiat Oncol Biol Phys; 2002 May 1;53(1):43-51
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  • PURPOSE: To describe the rationale, technique, and early results of stereotactically guided conformal radiotherapy (SCRT) in the treatment of progressive or inoperable low-grade gliomas (LGGs) of childhood.
  • Tumors were located at the optic chiasm (n = 9), third ventricle (n = 2), hypothalamus, craniocervical junction, and pineal region (each n = 1).
  • Four patients received chemotherapy before SCRT.
  • Stereotactic coordinates and the tumor were defined by CT scanning with a fiducial system and MRI fusion.
  • The median tumor volume was 19.5 cm(3) (range 7.5-180).
  • The planning target volume was defined as the area of enhancing tumor plus a 5-10-mm margin.
  • The treatment technique consisted of 4 isocentric, noncoplanar, conformal, fixed fields.
  • Treatment was delivered in 30-33 daily fractions to a total dose of 50-55 Gy.
  • One child with optic chiasm glioma had local progression at 25 months, and 1 developed diffuse leptomeningeal disease without local progression at 27 months.
  • The frequency of delayed hypothalamic-pituitary axis dysfunction reflects tumor location adjacent to the hypothalamus and pituitary.
  • Additional follow-up is required to demonstrate that SCRT contributes to a reduction in treatment-related late toxicity, while maintaining the local control achieved with conventionally delivered RT in children with progressive LGGs.

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  • (PMID = 12007940.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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10. Schmiegelow M, Lassen S, Poulsen HS, Schmiegelow K, Hertz H, Andersson AM, Skakkebaek NE, Müller J: Gonadal status in male survivors following childhood brain tumors. J Clin Endocrinol Metab; 2001 Jun;86(6):2446-52
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  • The effect of radiotherapy (RT) and chemotherapy (CT) on gonadal function was assessed in males treated for a childhood brain tumor not directly involving the hypothalamus/pituitary (HP) axis in a population-based study with a long follow-up time.
  • All males <15 yr at the time of diagnosis (median: 9.0 yr, range: 0.8 to 14.9 yr) and diagnosed from January 1970 through February 1997 in the eastern part of Denmark and [gte]18 yr at the time of follow-up (median: 25.8 yr, range:18.5 to 39.3 yr) were included.
  • The median age at time of RT was 9.0 yr (range: 0.8 to 14.9 yr) and the median length of follow-up was 18 yr (range: 2.0 to 28.0 yr).
  • The biological effective dose of RT was determined to the HP region and to the spine and expressed in gray because the biological effective dose gives a means of expressing the biological effect on normal tissue of different dosage schedules in a uniform way.
  • In conclusion these data suggest that cranial irradiation for a childhood brain tumor may affect the HP axis, and adjuvant CT can reduce inhibin B indicating primary gonadal damage.
  • Thus, such patients may have normal or even low levels of FSH despite damage to the seminiferous epithelium, and because the fertility status by a semen analysis for psychological reasons can be difficult to obtain in this group of patients, we suggest inhibin B as the most useful direct serum marker of spermatogenesis in the follow-up of individuals who have received both cranial irradiation and gonadotoxic chemotherapy.
  • [MeSH-major] Brain Neoplasms / drug therapy. Brain Neoplasms / radiotherapy. Genitalia, Male / drug effects. Genitalia, Male / radiation effects. Prostatic Secretory Proteins
  • [MeSH-minor] Adult. Combined Modality Therapy / adverse effects. Follicle Stimulating Hormone / blood. Humans. Inhibins / blood. Luteinizing Hormone / blood. Male. Organ Size. Testis / pathology. Testosterone / blood

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  • [ErratumIn] J Clin Endocrinol Metab 2001 Aug;86(8):3967
  • (PMID = 11397837.001).
  • [ISSN] 0021-972X
  • [Journal-full-title] The Journal of clinical endocrinology and metabolism
  • [ISO-abbreviation] J. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Prostatic Secretory Proteins; 0 / beta-microseminoprotein; 3XMK78S47O / Testosterone; 57285-09-3 / Inhibins; 9002-67-9 / Luteinizing Hormone; 9002-68-0 / Follicle Stimulating Hormone
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11. Kaltsas GA, Powles TB, Evanson J, Plowman PN, Drinkwater JE, Jenkins PJ, Monson JP, Besser GM, Grossman AB: Hypothalamo-pituitary abnormalities in adult patients with langerhans cell histiocytosis: clinical, endocrinological, and radiological features and response to treatment. J Clin Endocrinol Metab; 2000 Apr;85(4):1370-6
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  • [Title] Hypothalamo-pituitary abnormalities in adult patients with langerhans cell histiocytosis: clinical, endocrinological, and radiological features and response to treatment.
  • Langerhans cell histiocytosis (LCH) is a rare disorder in which granulomatous deposits occur at multiple sites within the body, but which often involves the hypothalamo-pituitary axis (HPA).
  • Although diabetes insipidus (DI) is a well recognized complication, the frequency of anterior pituitary and other nonendocrine hypothalamic (NEH) involvement has not been well defined, particularly in adult patients with the disease.
  • We have evaluated the frequency and progression of LCH-related anterior pituitary and other NEH dysfunction and their responses to treatment in 12 adult patients with histologically proven LCH and DI.
  • Study evaluations comprised clinical (including formal psychometric assessment where appropriate), basal and dynamic pituitary function tests, and radiology with computed tomography and/or magnetic resonance imaging scanning.
  • Eleven patients received systemic treatment, and 5 patients received external beam radiotherapy confined to the HPA.
  • The median age at diagnosis of DI was 34 yr (range, 2-47 yr); DI was the presenting symptom in four patients, whereas the remaining eight each developed DI 1-20 yr (median, 2 yr) after the diagnosis of LCH.
  • Eight patients developed one or more anterior pituitary hormonal deficiencies at a median of 4.5 yr (range, 2-22 yr) after the diagnosis of DI: GH deficiency developed in eight patients (median, 2 yr; range, 2-22 yr), FSH-LH deficiency in 7 patients (median, 7 yr; range, 2-22 yr), and TSH and ACTH deficiency in five patients (median, 10 yr; range, 3-16 and 3-19 yr), respectively; five patients developed panhypopituitarism.
  • In addition, seven patients with anterior pituitary dysfunction also developed symptoms of other NEH dysfunctions at a median of 10 yr (range, 1-23 yr): five morbid obesity (body mass index, >35), five short term memory deficits, four sleeping disorders, two disorders of thermoregulation, and one adipsia.
  • All patients developed disease outside of the hypothalamus during the course of the study, and no fluctuation of disease activity in the HPA region was noted.
  • Radiological examination of the HPA was abnormal in each of the eight patients with anterior pituitary involvement and in the seven patients with NEH dysfunction (one or more abnormalities): seven had thickening of the infundibulum, and one had hypothalamic and thalamic signal changes.
  • All patients who had a magnetic resonance imaging scan had absence of the bright spot of the posterior pituitary on the T1-weighted sequences, and in four patients with DI and normal anterior pituitary function this was the only abnormality.
  • The five patients who received radiotherapy to the HPA achieved a partial or complete radiological response, and there was no evidence of tumor progression in this region.
  • No form of therapy, including chemotherapy, improved any established hormonal deficiencies or symptoms of NEH.
  • In summary, in our adult patients with hypothalamic LCH and DI, anterior pituitary hormonal deficiencies developed in 8 of 12 patients; these occurred over the course of 20 yr.
  • In addition, symptoms of NEH dysfunction developed in up to 90% of such patients and complicated management.
  • Radiotherapy may be useful in achieving local control of tumor, but established anterior, posterior pituitary, and other NEH dysfunctions do not improve in response to current treatment protocols.
  • Patients with LCH and DI, particularly those with multisystem disease and a structural lesion on radiology, should undergo regular and prolonged endocrine assessment to establish anterior pituitary deficiency and provide appropriate hormonal replacement.
  • [MeSH-major] Histiocytosis, Langerhans-Cell / physiopathology. Histiocytosis, Langerhans-Cell / therapy. Hypothalamus / physiopathology. Pituitary Gland / physiopathology
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Agents / therapeutic use. Bone Diseases / etiology. Child, Preschool. Diabetes Insipidus / diagnosis. Diabetes Insipidus / etiology. Female. Humans. Hypopituitarism / etiology. Hypothalamic Diseases / etiology. Magnetic Resonance Imaging. Male. Middle Aged. Pituitary Hormones, Anterior / deficiency. Radiotherapy. Tomography, X-Ray Computed

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  • (PMID = 10770168.001).
  • [ISSN] 0021-972X
  • [Journal-full-title] The Journal of clinical endocrinology and metabolism
  • [ISO-abbreviation] J. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Pituitary Hormones, Anterior
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12. Dong JC, Zhao FD, Xie JY: [Effects of milkvetch root on neuro-endocrino-immune network in asthma model rat]. Zhongguo Zhong Xi Yi Jie He Za Zhi; 2007 Jul;27(7):619-22
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  • The corticotropin releasing hormone (CRH) mRNA expression in hypothalamus was tested by Realtime-PCR, serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected with radioimmunoassay, serum IL-6, IL-4, IFN-gamma determined with enzyme-linked immunosorbent assay, and the lung tissue pathology was examined by hematoxylin and eosin staining.
  • No significant difference was found in comparison of pathological changes of lung tissue among the groups.
  • CONCLUSION: Rats suffered from repeated asthmatic attack have some disorders in indexes of NEI, MR could enhance the function of hypothalamic-pituitary-adrenal cortex axis and adjust the balance of Th1 and Th2 cytokines to alleviate the inflammation of asthma.

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  • (PMID = 17717922.001).
  • [ISSN] 1003-5370
  • [Journal-full-title] Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine
  • [ISO-abbreviation] Zhongguo Zhong Xi Yi Jie He Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Drugs, Chinese Herbal
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13. Covelli V, Passeri ME, Leogrande D, Jirillo E, Amati L: Drug targets in stress-related disorders. Curr Med Chem; 2005;12(15):1801-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Drug targets in stress-related disorders.
  • Adrenocorticotropin hormone (ACTH) is a product of the hypothalamus-pituitary adrenal axis (HPAA) which stimulates secretion of corticosteroids from adrenals.
  • However, cytokines are locally produced in the brain, especially in the hypothalamus, thus contributing to the development of anorexic, pyrogenic, somnogenic and behavioural effects.
  • Phobic disorders and migraine without aura (MWA) represent examples of stress-related disorders in which phagocytic immune deficits, endotoxemia and exaggerated levels of proinflammatory cytokines [Tumor Necrosis Factor-alpha (TNF- alpha), and interleukin- 1 beta] have been detected.
  • Chronic Fatigue Syndrome (CFS) is a disorder whose etiology and pathogenesis are still unknown.
  • Finally, in a series of recent therapeutic trials several immunomodulating agents have been used, such as staphypan Berna, lactic acid bacteria, kuibitang and intravenous immunoglobulin.
  • In conclusion, it seems that major drug targets in stress-related disorders are immune cells in terms of inhibition of proinflammatory cytokines and modulation of Th responses.
  • [MeSH-major] Fatigue Syndrome, Chronic / drug therapy. Migraine Disorders / drug therapy. Phobic Disorders / drug therapy. Stress, Psychological / drug therapy

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  • (PMID = 16029148.001).
  • [ISSN] 0929-8673
  • [Journal-full-title] Current medicinal chemistry
  • [ISO-abbreviation] Curr. Med. Chem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Netherlands
  • [Number-of-references] 119
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14. Goebel MU, Baase J, Pithan V, Exton M, Saller B, Schedlowski M, Limmroth V: Acute interferon beta-1b administration alters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects. Psychoneuroendocrinology; 2002 Nov;27(8):881-92
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  • [Title] Acute interferon beta-1b administration alters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects.
  • Interferon beta (IFN beta-1b) treatment is the therapy of choice in patients suffering from relapsing remitting or secondary chronic progressive multiple sclerosis.
  • While typical adverse events of IFN beta-1b treatment such as flu-like symptoms or fatigue are well studied, little is known about the acute changes in the immune and neuroendocrine system.
  • Moreover, we determined heart rate, blood pressure, body temperature, leukocyte and lymphocyte subsets and plasma levels of interleukin (IL)-1 beta, IL-6, IL-10 and tumor necrosis factor (TNF)-alpha.
  • At the same time, IL-6, IL-10 and TNF-alpha plasma levels showed an overall increase.
  • Overall, cytokine administration exerts strong stimulatory effects on the hypothalamic-pituitary-adrenal (HPA)-axis that may contribute to the side effects of IFN beta-1b therapy and affect the efficacy of IFN beta-1b treatment.
  • [MeSH-major] Adrenal Glands / drug effects. Cytokines / blood. Hypothalamus / drug effects. Interferon-beta / pharmacology. Leukocyte Count. Pituitary Gland / drug effects
  • [MeSH-minor] Adjuvants, Immunologic / pharmacology. Adult. Blood Pressure / drug effects. Body Temperature / drug effects. Cross-Over Studies. Flow Cytometry. Heart Rate / drug effects. Humans. Hydrocortisone / blood. Interferon beta-1b. Interleukin-10 / blood. Interleukin-6 / blood. Kinetics. Lymphocyte Subsets. Male. Placebos. Recombinant Proteins / pharmacology. Tumor Necrosis Factor-alpha / analysis

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  • (PMID = 12383450.001).
  • [ISSN] 0306-4530
  • [Journal-full-title] Psychoneuroendocrinology
  • [ISO-abbreviation] Psychoneuroendocrinology
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Cytokines; 0 / Interleukin-6; 0 / Placebos; 0 / Recombinant Proteins; 0 / Tumor Necrosis Factor-alpha; 130068-27-8 / Interleukin-10; 145155-23-3 / Interferon beta-1b; 77238-31-4 / Interferon-beta; WI4X0X7BPJ / Hydrocortisone
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15. Rothman MS, Wierman ME: The role of gonadotropin releasing hormone in normal and pathologic endocrine processes. Curr Opin Endocrinol Diabetes Obes; 2007 Aug;14(4):306-10
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • PURPOSE OF REVIEW: Gonadotropin releasing hormone is the hypothalamic hormone that activates pituitary gonadotropin production and, ultimately, determines reproductive competence.
  • This review will highlight advances in the basic biology of the gonadotropin releasing hormone neuron that give insight into disorders of pubertal development, and clinical studies with gonadotropin releasing hormone analogs in infertility and prostate cancer treatment.
  • Clarification of the advantages and disadvantages of gonadotropin releasing hormone analog use in ovulation induction may improve the cost and success of infertility treatment.
  • Insight into long-term effects of gonadotropin releasing hormone analogs in prostate cancer may lead to directed therapies to combat these consequences.
  • [MeSH-major] Gonadotropin-Releasing Hormone / agonists. Gonadotropin-Releasing Hormone / antagonists & inhibitors. Infertility / drug therapy. Prostatic Neoplasms / drug therapy
  • [MeSH-minor] Endocrine Glands / metabolism. Humans. Hypothalamus / metabolism. Kisspeptins. Male. Receptors, G-Protein-Coupled / metabolism. Signal Transduction. Tumor Suppressor Proteins / metabolism

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  • (PMID = 17940457.001).
  • [ISSN] 1752-2978
  • [Journal-full-title] Current opinion in endocrinology, diabetes, and obesity
  • [ISO-abbreviation] Curr Opin Endocrinol Diabetes Obes
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / KISS1 protein, human; 0 / Kisspeptins; 0 / Receptors, G-Protein-Coupled; 0 / Tumor Suppressor Proteins; 33515-09-2 / Gonadotropin-Releasing Hormone
  • [Number-of-references] 40
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16. Giavoli C, Libé R, Corbetta S, Ferrante E, Lania A, Arosio M, Spada A, Beck-Peccoz P: Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients. J Clin Endocrinol Metab; 2004 Nov;89(11):5397-401
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  • [Title] Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients.
  • The aim of the study was to evaluate the hypothalamus-pituitary-adrenal (HPA) axis in patients (nine males, three females; mean age +/- sem 51 +/- 2 yr) with adult-onset GH deficiency (GHD) due to surgically treated pituitary tumors with preserved HPA function and without evidence of tumor recurrence before and during recombinant human (rh) GH replacement therapy (duration 31 +/- 6 months).
  • HPA function was assessed by urinary free cortisol and morning serum cortisol levels as well as cortisol responses to 1 mug ACTH test (n = 7 patients) or insulin tolerance test (n = 5 patients) before and during rhGH therapy, the cut-off for the diagnosis of hypoadrenalism being a cortisol peak less than 18 microg/dl (<500 nmol/liter) after stimulatory tests.
  • Serum cortisol and urinary free cortisol levels were significantly lower on therapy than before [7.6 +/- 0.8 vs. 11.5 +/- 0.9 microg/dl (208 +/- 22 vs. 317 +/- 24 nmol/liter), P < 0.01, and 19.6 +/- 2.5 vs. 32.2 +/- 3.2 microg per 24 h (54 +/- 7 vs. 89 +/- 9 nmol per 24 h), P < 0.05, respectively], whereas no change in cortisol-binding globulin levels was observed.
  • Cortisol peak after either ACTH test or insulin tolerance test was lower on rhGH therapy than before [15.9 +/- 1.5 vs. 20.2 +/- 1.1 microg/dl (437 +/- 43 vs. 557 +/- 31), P = 0.01, and 13.1 +/- 2.6 vs. 20.4 +/- 1.4 microg/dl (362 +/- 71 vs. 564 +/- 37 nmol/liter), P = 0.03, respectively].
  • Therefore, the reassessment of HPA function in GHD patients during rhGH therapy is mandatory.
  • [MeSH-major] Hormone Replacement Therapy. Human Growth Hormone / deficiency. Human Growth Hormone / therapeutic use. Hypothalamo-Hypophyseal System / drug effects. Pituitary-Adrenal System / drug effects

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  • (PMID = 15531488.001).
  • [ISSN] 0021-972X
  • [Journal-full-title] The Journal of clinical endocrinology and metabolism
  • [ISO-abbreviation] J. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 12629-01-5 / Human Growth Hormone; EC 1.1.1.146 / 11-beta-Hydroxysteroid Dehydrogenases
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17. Steinbok P, Hukin J: Intracystic treatments for craniopharyngioma. Neurosurg Focus; 2010 Apr;28(4):E13
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  • [Title] Intracystic treatments for craniopharyngioma.
  • Craniopharyngioma is a benign tumor histopathologically and in theory should be curable by radical resection.
  • In practice, this tumor behaves like a chronic disease, with many issues related to the effect of the tumor itself and the various treatments on the adjacent structures, such as the pituitary stalk and gland, hypothalamus, visual apparatus, and suprasellar arteries.
  • In this paper, the role of intracystic therapies is reviewed, with the major focus on intracystic bleomycin and interferon-alpha.
  • [MeSH-major] Antibiotics, Antineoplastic / administration & dosage. Antibiotics, Antineoplastic / therapeutic use. Bleomycin / therapeutic use. Craniopharyngioma / drug therapy. Immunologic Factors / therapeutic use. Interferon-alpha / therapeutic use. Pituitary Neoplasms / drug therapy
  • [MeSH-minor] Combined Modality Therapy. Humans. Injections, Intralesional. Radiotherapy, Conformal. Treatment Outcome

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  • (PMID = 20367357.001).
  • [ISSN] 1092-0684
  • [Journal-full-title] Neurosurgical focus
  • [ISO-abbreviation] Neurosurg Focus
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Immunologic Factors; 0 / Interferon-alpha; 11056-06-7 / Bleomycin
  • [Number-of-references] 51
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18. Filopanti M, Lania AG, Spada A: Pharmacogenetics of D2 dopamine receptor gene in prolactin-secreting pituitary adenomas. Expert Opin Drug Metab Toxicol; 2010 Jan;6(1):43-53
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  • [Title] Pharmacogenetics of D2 dopamine receptor gene in prolactin-secreting pituitary adenomas.
  • IMPORTANCE OF THE FIELD: Dopamine-agonists are the treatment of choice of prolactin-secreting pituitary adenomas (PRL-omas).
  • The dopamine-agonist cabergoline (CB), normalizes prolactin and reduces tumor size in about 80 - 90% of patients.
  • This review describes the DRD2 polymorphisms, their functional effects, and their impact on susceptibility and response to dopamine-agonists treatment.
  • WHAT THE READER WILL GAIN: This review deals with the connection between DRD2 polymorphisms and PRL-oma treatment and suggests hypotheses for further studies.
  • Further studies, including pituitary and hypothalamus in vivo determination of DRD2 binding according to DRD2 genotypes, investigation of possible post-receptorial mechanisms involved, as well as population studies in collaboration with psychiatrists and neurologists, are needed.
  • [MeSH-major] Dopamine Agonists / pharmacokinetics. Dopamine Agonists / therapeutic use. Prolactinoma / drug therapy. Prolactinoma / genetics. Receptors, Dopamine D2 / drug effects. Receptors, Dopamine D2 / genetics

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  • (PMID = 19929252.001).
  • [ISSN] 1744-7607
  • [Journal-full-title] Expert opinion on drug metabolism & toxicology
  • [ISO-abbreviation] Expert Opin Drug Metab Toxicol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Dopamine Agonists; 0 / Receptors, Dopamine D2
  • [Number-of-references] 67
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19. Rometo AM, Krajewski SJ, Voytko ML, Rance NE: Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J Clin Endocrinol Metab; 2007 Jul;92(7):2744-50
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  • OBJECTIVES: Our objective was to map the location of neurons expressing kisspeptin gene (KiSS-1) transcripts in the human hypothalamus and determine whether menopause is associated with changes in the size and gene expression of kisspeptin neurons.
  • SUBJECTS: Hypothalamic tissues were collected at autopsy from eight premenopausal and nine postmenopausal women and from 42 young cynomolgus monkeys in various endocrine states.
  • [MeSH-major] Pituitary Gland, Posterior / physiology. Postmenopause / physiology. Tumor Suppressor Proteins / genetics. Tumor Suppressor Proteins / metabolism
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Animals. Arcuate Nucleus of Hypothalamus / cytology. Arcuate Nucleus of Hypothalamus / physiology. Estrogen Replacement Therapy. Estrogens / metabolism. Estrogens / pharmacology. Estrogens / therapeutic use. Feedback, Physiological / drug effects. Feedback, Physiological / physiology. Female. Gene Expression / drug effects. Gene Expression / physiology. Humans. Hypertrophy. Kisspeptins. Macaca fascicularis. Middle Aged. Neurons / physiology. Ovariectomy. Progesterone / pharmacology. Progesterone / therapeutic use. RNA, Messenger / metabolism

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  • (PMID = 17488799.001).
  • [ISSN] 0021-972X
  • [Journal-full-title] The Journal of clinical endocrinology and metabolism
  • [ISO-abbreviation] J. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Grant] United States / NIA NIH HHS / AG / AG-09214; United States / NIA NIH HHS / AG / T32 AG007434
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Estrogens; 0 / KISS1 protein, human; 0 / Kisspeptins; 0 / RNA, Messenger; 0 / Tumor Suppressor Proteins; 4G7DS2Q64Y / Progesterone
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20. Hug EB, Adams J, Fitzek M, De Vries A, Munzenrider JE: Fractionated, three-dimensional, planning-assisted proton-radiation therapy for orbital rhabdomyosarcoma: a novel technique. Int J Radiat Oncol Biol Phys; 2000 Jul 1;47(4):979-84
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Fractionated, three-dimensional, planning-assisted proton-radiation therapy for orbital rhabdomyosarcoma: a novel technique.
  • However, conventional photon-radiation treatment, as part of multimodality therapy, results in varying degrees of long-term functional and cosmetic side effects.
  • This report introduces external beam proton radiation therapy (PRT) as a conformal, three-dimensional planned radiation technique for this disease, analyzes normal tissue dosimetry, and describes the technique's application in the first 2 patients.
  • MATERIAL AND METHODS: Between January 1995 and February 1996, 2 patients underwent PRT following biopsy and chemotherapy for orbital rhabdomyosarcoma.
  • Fifty and 55 Cobalt Gray Equivalent (CGE) were delivered to the gross tumor volume and 40 CGE to clinical target volumes in both patients.
  • Dose-volume histograms were obtained for target and nontarget regions, including lens, bony orbit, pituitary gland, optic chiasm, optic nerves, lacrimal gland, and ipsilateral frontal and temporal lobes.
  • Visual acuity remains excellent, without signs of cataract formation; pituitary function is normal; cosmetically, only mild enophthalmos is noticeable.
  • Fifty percent of lacrimal gland volume received less than 36% of the prescribed dose and 50% of the volume of the optic chiasm, pituitary gland, and hypothalamus were restricted to less than 2%.
  • The steep dose gradient beyond the orbit minimizes irradiation of normal brain parenchyma, with almost complete sparing of the pituitary gland.
  • Reduction of integral irradiation exposure of the periorbital region will, hopefully, reduce the risk of second malignancy later in life.
  • Reduced radiation dose to specific organs in close proximity to, but not part of the target region promises improved functional outcome and better cosmesis for childhood cancer survivors.
  • [MeSH-major] Orbital Neoplasms / radiotherapy. Protons / therapeutic use. Radiotherapy, Conformal / methods. Rhabdomyosarcoma / radiotherapy
  • [MeSH-minor] Child. Dose Fractionation. Female. Follow-Up Studies. Humans. Male. Orbit / radiography. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 10863068.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Protons
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