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1. Khong JJ, Muecke J: Complications of mitomycin C therapy in 100 eyes with ocular surface neoplasia. Br J Ophthalmol; 2006 Jul;90(7):819-22
Hazardous Substances Data Bank. MITOMYCIN C .

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  • [Title] Complications of mitomycin C therapy in 100 eyes with ocular surface neoplasia.
  • AIM: To determine the complications associated with mitomycin C (MMC) in the treatment of ocular surface neoplasia.
  • Outcome measures included complications of MMC and the treatment required for these complications.
  • RESULTS: One to three 7 day cycles of topical MMC 0.04% four times a day were given to 59 eyes with localised corneal-conjunctival intraepithelial neoplasia (CIN), 19 eyes with diffuse CIN, six eyes with recurrent CIN, one eye with ocular surface squamous cell carcinoma, three eyes with primary acquired melanosis (PAM) with atypia, nine eyes with conjunctival malignant melanoma (MM), two eyes with sebaceous carcinoma with pagetoid spread, and one eye with recurrent atypical fibroxanthoma.
  • 31 (34%) cases developed an allergic reaction to MMC and 14 (14%) eyes had epiphora secondary to punctal stenosis at a mean follow up period of 26.5 months.
  • CONCLUSION: In the largest study looking at complications of topical MMC in the treatment of ocular surface neoplasia, allergic reaction and punctal stenosis are relatively common.
  • [MeSH-major] Antibiotics, Antineoplastic / adverse effects. Drug Hypersensitivity / etiology. Eye Neoplasms / drug therapy. Mitomycin / adverse effects
  • [MeSH-minor] Adenocarcinoma, Sebaceous / drug therapy. Carcinoma in Situ / drug therapy. Carcinoma, Squamous Cell / drug therapy. Conjunctival Neoplasms / drug therapy. Corneal Diseases / drug therapy. Female. Follow-Up Studies. Histiocytoma, Benign Fibrous / drug therapy. Humans. Lacrimal Apparatus Diseases / chemically induced. Lacrimal Duct Obstruction / chemically induced. Male. Melanoma / drug therapy. Melanosis / drug therapy. Retrospective Studies

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  • [CommentIn] Br J Ophthalmol. 2006 Jul;90(7):807-9 [16782942.001]
  • (PMID = 16672325.001).
  • [ISSN] 0007-1161
  • [Journal-full-title] The British journal of ophthalmology
  • [ISO-abbreviation] Br J Ophthalmol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 50SG953SK6 / Mitomycin
  • [Other-IDs] NLM/ PMC1857172
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2. LaMontagne K, Littlewood-Evans A, Schnell C, O'Reilly T, Wyder L, Sanchez T, Probst B, Butler J, Wood A, Liau G, Billy E, Theuer A, Hla T, Wood J: Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Cancer Res; 2006 Jan 1;66(1):221-31
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  • We show here that FTY720 has antiangiogenic activity, potently abrogating VEGF- and S1P-induced angiogenesis in vivo in growth factor implant and corneal models.
  • FTY720 administration tended to inhibit primary and significantly inhibited metastatic tumor growth in a mouse model of melanoma growth.
  • These data show that functional antagonism of vascular S1P receptors by FTY720 potently inhibits angiogenesis; therefore, this may provide a novel therapeutic approach for pathologic conditions with dysregulated angiogenesis.
  • [MeSH-major] Melanoma, Experimental / blood supply. Melanoma, Experimental / drug therapy. Propylene Glycols / pharmacology. Receptors, Lysosphingolipid / antagonists & inhibitors
  • [MeSH-minor] Animals. Calcium / metabolism. Cell Growth Processes / drug effects. Cell Movement / drug effects. Cornea / blood supply. Endothelial Cells / drug effects. Endothelial Cells / enzymology. Female. Fingolimod Hydrochloride. Humans. Mice. Mitogen-Activated Protein Kinases / metabolism. Neovascularization, Pathologic / drug therapy. Neovascularization, Physiologic / drug effects. Phosphorylation. Phthalazines / pharmacology. Pyridines / pharmacology. Sphingosine / analogs & derivatives. Vascular Endothelial Growth Factor A / antagonists & inhibitors. Vascular Endothelial Growth Factor Receptor-2 / metabolism

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  • (PMID = 16397235.001).
  • [ISSN] 0008-5472
  • [Journal-full-title] Cancer research
  • [ISO-abbreviation] Cancer Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Phthalazines; 0 / Propylene Glycols; 0 / Pyridines; 0 / Receptors, Lysosphingolipid; 0 / Vascular Endothelial Growth Factor A; 5DX9U76296 / vatalanib; EC 2.7.10.1 / Vascular Endothelial Growth Factor Receptor-2; EC 2.7.11.24 / Mitogen-Activated Protein Kinases; G926EC510T / Fingolimod Hydrochloride; NGZ37HRE42 / Sphingosine; SY7Q814VUP / Calcium
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3. Shields CL, Shields JA, Armstrong T: Management of conjunctival and corneal melanoma with surgical excision, amniotic membrane allograft, and topical chemotherapy. Am J Ophthalmol; 2001 Oct;132(4):576-8
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  • [Title] Management of conjunctival and corneal melanoma with surgical excision, amniotic membrane allograft, and topical chemotherapy.
  • PURPOSE: To illustrate a novel method of management for extensive conjunctival and corneal melanoma.
  • A 40-year-old Caucasian woman presented with a large, diffuse conjunctival melanoma involving 6 clock hours of the limbus.
  • The remaining bulbar conjunctiva and the entire corneal epithelium were affected by diffuse, flat melanosis.
  • RESULTS: The conjunctival melanoma was completely resected microsurgically in one piece without disrupting the tumor.
  • The corneal melanosis was subsequently treated with topical mitomycin C eyedrops.
  • At 8 months follow-up, the conjunctiva and the cornea were completely healed with resolution of all pigment and 20/20 visual acuity.
  • CONCLUSION: Preliminary evidence suggests that combined therapeutic approaches, consisting of extensive tumor removal, cryotherapy, amniotic membrane allograft, and topical mitomyin C, can be effective in the management of diffuse conjunctival and corneal melanoma arising from primary acquired melanosis.
  • [MeSH-major] Amnion / transplantation. Antibiotics, Antineoplastic / therapeutic use. Conjunctival Neoplasms / therapy. Corneal Diseases / therapy. Melanoma / therapy. Melanosis / therapy. Mitomycin / therapeutic use. Ophthalmologic Surgical Procedures
  • [MeSH-minor] Adult. Combined Modality Therapy. Female. Humans. Transplantation, Homologous

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  • (PMID = 11589886.001).
  • [ISSN] 0002-9394
  • [Journal-full-title] American journal of ophthalmology
  • [ISO-abbreviation] Am. J. Ophthalmol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 50SG953SK6 / Mitomycin
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4. Russell HC, Chadha V, Lockington D, Kemp EG: Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: a 10-year review of treatment outcomes and complications. Br J Ophthalmol; 2010 Oct;94(10):1316-21
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  • [Title] Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: a 10-year review of treatment outcomes and complications.
  • The aim of this study is to determine outcomes and complications following such treatment.
  • METHODS: This study is a retrospective review of patients treated with topical MMC for ocular surface neoplasia, including primary acquired melanosis (PAM), melanoma, corneal-conjunctival intraepithelial neoplasia (CCIN), squamous cell carcinoma (SCC) and sebaceous gland carcinoma (SGC).
  • 21 received MMC as primary therapy and 37 as surgical adjuvant.
  • The regimen was 0.04% MMC four times a day for 3 weeks on, 3 weeks off, 3 weeks on, with topical steroid and lubricants throughout.
  • Overall, 26% developed recurrent disease at a mean of 13 months post treatment.
  • Recurrence rates by pathology were 20% PAM, 25% melanoma, 0% CCIN, 67% SCC and 57% SGC.
  • Short-term complications occurred in 52%, but only 7% required treatment cessation.
  • Long-term complications such as persisting keratoconjunctivitis, epiphora and corneal problems, occurred in 31%.
  • CONCLUSION: The results confirm the effectiveness of topical MMC chemotherapy in the management of ocular surface neoplasia.
  • Self-limiting short-term complications were common; however, limbal stem cell deficiency appears to be a significant long-term complication of treatment, occurring in 12%.
  • [MeSH-major] Antibiotics, Antineoplastic / administration & dosage. Eye Neoplasms / drug therapy. Mitomycin / administration & dosage. Sebaceous Gland Neoplasms / drug therapy
  • [MeSH-minor] Administration, Topical. Adult. Aged. Aged, 80 and over. Chemotherapy, Adjuvant. Female. Humans. Male. Middle Aged. Neoplasm Recurrence, Local / etiology. Retrospective Studies. Treatment Outcome. Young Adult

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  • (PMID = 20530655.001).
  • [ISSN] 1468-2079
  • [Journal-full-title] The British journal of ophthalmology
  • [ISO-abbreviation] Br J Ophthalmol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 50SG953SK6 / Mitomycin
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5. Demirci H, McCormick SA, Finger PT: Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: clinical experience with histopathologic observations. Arch Ophthalmol; 2000 Jul;118(7):885-91
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  • [Title] Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: clinical experience with histopathologic observations.
  • OBJECTIVES: To clinically evaluate topical mitomycin chemotherapy in patients with diffuse, multifocal, or recurrent primary acquired melanosis with atypia and/or conjunctival malignant melanoma and to histopathologically study ocular tissue samples obtained before and after treatment.
  • METHODS: Chemotherapy with topical mitomycin, 0.04% 4 times daily, was administered for 28 days as the primary and only treatment in 7 patients (after biopsy) and for 7 days as adjuvant therapy to excision and cryotherapy in 5 patients.
  • Five patients developed subconjunctival recurrences, for which 2 underwent orbital exenteration and 3 were treated conservatively.
  • Histopathologic specimens of conjunctival, adnexal, and ocular tissues obtained before and after chemotherapy were evaluated.
  • RESULTS: Regression of tumor was observed in 11 patients with primary or adjuvant topical mitomycin chemotherapy.
  • One patient with nodular melanoma was resistant to mitomycin chemotherapy.
  • Two patients with primary treatment and 2 with adjuvant treatment developed subconjunctival recurrence.
  • In patients with recurrent malignant melanoma, the deeper layers of the lamina propria were involved, with sparing of the epithelium and superficial lamina propria.
  • Transient keratoconjunctivitis was observed in all patients during treatment.
  • In evaluation of the exenteration specimens, corneal, scleral, episcleral, retinal, and anterior structures were within normal limits.
  • CONCLUSIONS: Topical mitomycin chemotherapy was found to induce regression of conjunctival melanoma and primary acquired melanosis with atypia.
  • When mitomycin chemotherapy was used as an adjuvant to excision and cryotherapy, 2 (40%) of 5 patients experienced tumor recurrence at a mean of 4.3 years' follow-up.
  • Our histopathologic findings demonstrated a long-term mitomycin chemotherapy-related effect on the conjunctiva.
  • The pattern of effect and location of recurrent disease suggest that this regimen of topical mitomycin chemotherapy was most effective for superficial tumors.
  • Although subconjunctival or orbital recurrences were noted, topical mitomycin chemotherapy warrants further investigation as an alternative treatment for primary acquired melanosis with atypia and conjunctival malignant melanoma.
  • [MeSH-major] Antibiotics, Antineoplastic / therapeutic use. Conjunctival Neoplasms / drug therapy. Melanoma / drug therapy. Melanosis / drug therapy. Mitomycin / therapeutic use
  • [MeSH-minor] Administration, Topical. Adult. Aged. Atrophy / chemically induced. Chemotherapy, Adjuvant. Conjunctiva / drug effects. Conjunctiva / pathology. Cryotherapy. Drug Evaluation. Female. Humans. Keratoconjunctivitis / chemically induced. Male. Middle Aged. Neoplasm Recurrence, Local. Ophthalmic Solutions / administration & dosage. Ophthalmic Solutions / therapeutic use. Treatment Outcome

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  • (PMID = 10900099.001).
  • [ISSN] 0003-9950
  • [Journal-full-title] Archives of ophthalmology (Chicago, Ill. : 1960)
  • [ISO-abbreviation] Arch. Ophthalmol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Ophthalmic Solutions; 50SG953SK6 / Mitomycin
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6. Kurli M, Finger PT: Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: 12 years' experience. Graefes Arch Clin Exp Ophthalmol; 2005 Nov;243(11):1108-14
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  • [Title] Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: 12 years' experience.
  • PURPOSE: To report 12-year follow-up experience with topical mitomycin chemotherapy for diffuse and multifocal primary acquired melanosis (PAM) with atypia and conjunctival melanoma.
  • Mitomycin was a primary treatment for residual epithelial disease in ten patients (eight with PAM with atypia and two with conjunctival melanoma) and as an adjuvant to excision and cryotherapy in six with conjunctival malignant melanoma.
  • Primary treatments consisted of mitomycin 0.04% qid for 28 days (two 14-day cycles) and for 7 consecutive days as adjuvant therapy.
  • RESULTS: Sixteen patients were followed for a mean 81 months (range 13-144 months) after treatment.
  • All tumors responded to chemotherapy.
  • Recurrence was noted in eight (three adjuvant and five primary treatment patients).
  • The mean time to recurrence was 36.9 months.
  • The short-term mitomycin-related complications included transient keratoconjunctivitis (n=14), severe keratoconjunctivitis (n=1) and one corneal abrasion with scar formation.
  • The long-term complications included pannus (n=2) and corneal haze (n=1).
  • Three patients died, one of metastatic conjunctival melanoma.
  • CONCLUSIONS: Conjunctival melanoma and PAM responded to mitomycin 0.04% topical chemotherapy; subepithelial nests appeared resistant to treatment.
  • Treatment-related complications were acceptable.
  • In this series, as primary and adjuvant therapy, topical mitomycin yielded an overall recurrence rate of 50%.
  • [MeSH-major] Antibiotics, Antineoplastic / therapeutic use. Conjunctival Neoplasms / drug therapy. Melanoma / drug therapy. Melanosis / drug therapy. Mitomycin / therapeutic use
  • [MeSH-minor] Administration, Topical. Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Neoplasm Recurrence, Local / pathology. Treatment Outcome

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  • (PMID = 15940485.001).
  • [ISSN] 0721-832X
  • [Journal-full-title] Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
  • [ISO-abbreviation] Graefes Arch. Clin. Exp. Ophthalmol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 50SG953SK6 / Mitomycin
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7. Finger PT, Sedeek RW, Chin KJ: Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex. Am J Ophthalmol; 2008 Jan;145(1):124-129
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  • [Title] Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex.
  • PURPOSE: To report on topical interferon alfa-2b for conjunctival malignant melanoma (CMM) and primary acquired melanosis with atypia (PAM).
  • METHODS: Five eyes of five consecutive patients with biopsy-proven malignant melanoma were treated with topical interferon alfa-2b as treatment for primary or recurrent disease.
  • One drop of interferon alfa-2b (1 million units/ml) was placed into the superior fornix four times daily for three months.
  • RESULTS: Five consecutive patients with conjunctival melanoma (American Joint Committee on Cancer-International Union Against Cancer stages T2 [n = 3] and T3 [n = 2]) were included.
  • Two patients had recurrent corneal tumors, eight and 13 months after local excision, cryotherapy, and topical mitomycin C therapy.
  • Two months after topical interferon alfa-2b treatment, the lesions regressed without side effects.
  • This melanoma did not respond to topical interferon alfa-2b nor did the patient tolerate treatment (keratoconjunctivitis).
  • CONCLUSIONS: We present evidence that conjunctival and corneal melanoma regresses after exposure to topical interferon alfa-2b.
  • A larger-scale longer-term study must evaluate the long-term efficacy and safety of this therapy.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Conjunctival Neoplasms / drug therapy. Interferon-alpha / administration & dosage. Melanoma / drug therapy. Melanosis / drug therapy
  • [MeSH-minor] Administration, Topical. Aged, 80 and over. Female. Humans. Male. Middle Aged. Ophthalmic Solutions / administration & dosage. Recombinant Proteins. Retrospective Studies. Treatment Outcome

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  • (PMID = 17981257.001).
  • [ISSN] 0002-9394
  • [Journal-full-title] American journal of ophthalmology
  • [ISO-abbreviation] Am. J. Ophthalmol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Ophthalmic Solutions; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b
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8. Chalasani R, Giblin M, Conway RM: Role of topical chemotherapy for primary acquired melanosis and malignant melanoma of the conjunctiva and cornea: review of the evidence and recommendations for treatment. Clin Exp Ophthalmol; 2006 Sep-Oct;34(7):708-14
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  • [Title] Role of topical chemotherapy for primary acquired melanosis and malignant melanoma of the conjunctiva and cornea: review of the evidence and recommendations for treatment.
  • Surgical excision with cryotherapy is a well-established treatment option for malignant melanoma or primary acquired melanosis (PAM) with atypia of the conjunctiva and cornea.
  • Relevant studies were reviewed with regards to treatment regimen, rates of recurrence and metastasis, side effect profile and length of follow up.
  • A total of 22 and 16 unique cases of biopsy proven PAM with atypia and malignant melanoma, respectively, treated with topical MMC were identified.
  • Topical MMC was well tolerated and shows considerable promise, particularly in the treatment of diffuse PAM with atypia.
  • [MeSH-major] Antibiotics, Antineoplastic / therapeutic use. Conjunctival Neoplasms / drug therapy. Corneal Diseases / drug therapy. Eye Neoplasms / drug therapy. Melanoma / drug therapy. Melanosis / drug therapy. Mitomycin / therapeutic use

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  • (PMID = 16970772.001).
  • [ISSN] 1442-6404
  • [Journal-full-title] Clinical & experimental ophthalmology
  • [ISO-abbreviation] Clin. Experiment. Ophthalmol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 50SG953SK6 / Mitomycin
  • [Number-of-references] 31
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9. Kabasawa S, Murayama K, Tsuchida T, Tanaka K, Arai E, Yoneya S: [Case of corneally displaced malignant conjunctival melanoma]. Nippon Ganka Gakkai Zasshi; 2007 Feb;111(2):102-6
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  • [Title] [Case of corneally displaced malignant conjunctival melanoma].
  • BACKGROUND: We studied the clinicopathologic characteristics in a patient with malignant conjunctival melanoma associated with corneal invasion.
  • He developed recurrence and was referred to us.
  • Biomicroscopic examination revealed that there was a granular pigment lesion in the cornea.
  • The patient was diagnosed as having conjunctival melanoma with corneal invasion and treated with orbital exenteration and chemotherapy in our hospital.
  • Clinicopathologic tests revealed malignant melanoma cells invading through the bulbar conjunctiva and into the cornea.
  • Ultrastructural study by electron microscopy of the pigmented tumor cells in the cornea showed several lobations of the nuclei, a large active-appearing nucleolus, and an aberrant granular melanosomal morphology.
  • CONCLUSIONS: The infiltration of palpebral malignant conjunctival melanoma was limited to the epidermis of the cornea.
  • [MeSH-major] Conjunctival Neoplasms / pathology. Corneal Diseases / pathology. Eye Neoplasms / pathology. Melanoma / pathology
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Combined Modality Therapy. Humans. Male. Microscopy, Electron. Middle Aged. Neoplasm Invasiveness. Ophthalmologic Surgical Procedures. Prognosis

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  • (PMID = 17338327.001).
  • [ISSN] 0029-0203
  • [Journal-full-title] Nippon Ganka Gakkai zasshi
  • [ISO-abbreviation] Nippon Ganka Gakkai Zasshi
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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10. Chen JQ, Sun MX, Sha XY, Zhang P, Lin YS, Li H, Liu YM, Chen LS: [Management of corneo-conjunctival malignant melanoma with "no touch technique" surgical excision and corneoscleral lamellar keratoplasty]. Zhonghua Yan Ke Za Zhi; 2006 Jan;42(1):22-6
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  • [Title] [Management of corneo-conjunctival malignant melanoma with "no touch technique" surgical excision and corneoscleral lamellar keratoplasty].
  • OBJECTIVE: To study the management of "no touch technique" surgical excision and corneoscleral lamellar keratoplasty in the treatment of corneo-conjunctival malignant melanoma.
  • METHODS: Surgical excision for corneo-conjunctival malignant melanoma in six cases, from October 1989 to January 2004 in Zhongshan Ophthalmic Center, were performed.
  • The incision was outlined 4-6 mm outside the pigmented conjunctival mass, and 2 mm outside the corneal component.
  • All cases were subsequently treated with 0.01% thiotepa eyedrops and supplemental dacarbazine chemotherapy.
  • At the average 43.5 months follow-up time (14.6 years to 6 months), no evidences of local recurrence of malignant melanoma or distant metastasis were observed.
  • CONCLUSION: The clinical study suggests that using surgical excision of "no touch technique" to remove tumor in whole piece with corneoscleral lamellar keratoplasty is effective in the treatment of corneo-conjunctival malignant melanoma.
  • [MeSH-major] Conjunctival Neoplasms / surgery. Corneal Diseases / surgery. Corneal Transplantation / methods. Limbus Corneae / surgery. Melanosis / surgery
  • [MeSH-minor] Adult. Aged. Female. Follow-Up Studies. Humans. Male. Middle Aged. Treatment Outcome

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  • (PMID = 16638276.001).
  • [ISSN] 0412-4081
  • [Journal-full-title] [Zhonghua yan ke za zhi] Chinese journal of ophthalmology
  • [ISO-abbreviation] Zhonghua Yan Ke Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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11. Werschnik C, Lommatzsch PK: Long-term follow-up of patients with conjunctival melanoma. Am J Clin Oncol; 2002 Jun;25(3):248-55
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  • [Title] Long-term follow-up of patients with conjunctival melanoma.
  • Data from long-term follow-up examinations of patients with conjunctival melanoma are limited.
  • Therapeutic procedures were local excision, local excision followed by brachytherapy, local excision combined with cryotherapy, and local excision followed by either irradiation or cryotherapy and adjuvant mitomycin C (MMC) application.
  • Clinical parameters of the patients and the tumors were obtained and analyzed for their relation to tumor recurrence and death from metastatic melanoma using the multivariate Cox hazards modeling.
  • Patient age greater than 55 years, higher TNM category, and unfavorable tumor location (palpebral conjunctiva, fornix, caruncle, corneal stroma, eyelid) were identified as prognostic factors for death from metastatic melanoma.
  • Tumors with unfavorable location, higher TNM grade, and excision alone as initial therapy showed a higher cumulative probability of local relapse than favorably located (bulbar and limbal conjunctiva) tumors, lower TNM grade, and excision plus adjuvant therapy.
  • To minimize local recurrence rate surgical excision should be combined with an adjunctive procedure such as irradiation, cryotherapy, or local chemotherapy with MMC.
  • [MeSH-major] Conjunctival Neoplasms. Melanoma
  • [MeSH-minor] Combined Modality Therapy. Female. Follow-Up Studies. Humans. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Recurrence, Local. Prognosis. Proportional Hazards Models. Survival Analysis

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  • (PMID = 12040282.001).
  • [ISSN] 0277-3732
  • [Journal-full-title] American journal of clinical oncology
  • [ISO-abbreviation] Am. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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12. Singh N, Jani PD, Suthar T, Amin S, Ambati BK: Flt-1 intraceptor induces the unfolded protein response, apoptotic factors, and regression of murine injury-induced corneal neovascularization. Invest Ophthalmol Vis Sci; 2006 Nov;47(11):4787-93
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  • [Title] Flt-1 intraceptor induces the unfolded protein response, apoptotic factors, and regression of murine injury-induced corneal neovascularization.
  • PURPOSE: To determine whether Flt24K, a recombinant construct of domains 2 to 4 of VEGFR-1 (Flt) coupled with an endoplasmic reticulum retention signal (KDEL) can bind VEGFR-2 and induce apoptosis, unfolded protein response (UPR), and regression of injury-induced corneal neovascularization.
  • Human malignant melanoma cells (which express VEGFR-2 but not Flt), were transfected with pCMV.Flt24K, and lysates underwent immunoprecipitation with anti-FLT antibody, and Western blot analysis for VEGF and VEGFR-2.
  • RESULTS: The mean percentage area of corneal neovascularization in mice 3 weeks after corneal injury and 1 week after intrastromal injection of empty pCMV vector or pCMV.Flt24K was 55.4% +/- 2.7% vs. 19.3% +/- 6.1%, respectively (P < 0.001).
  • Apoptosis was observed in corneal neovascular endothelium in corneas treated with pCMV.Flt24K but not in the control.
  • CONCLUSIONS: The Flt24K intraceptor can bind VEGFR-2 within cells, induce the unfolded protein response in vitro and in vivo, elicit apoptosis of vascular endothelial cells in vivo, and induce regression of corneal neovascularization in vivo.
  • [MeSH-major] Apoptosis. Burns, Chemical / drug therapy. Corneal Neovascularization / drug therapy. DNA-Binding Proteins / metabolism. Endothelium, Vascular / pathology. Eye Burns / chemically induced. Nuclear Proteins / metabolism. Vascular Endothelial Growth Factor Receptor-1 / physiology
  • [MeSH-minor] Animals. Blotting, Western. Caspase 12 / metabolism. Caspase 3 / metabolism. Cornea / drug effects. Cornea / metabolism. Genetic Vectors. Humans. In Situ Nick-End Labeling. Mice. Mice, Inbred BALB C. Receptors, Peptide / physiology. Recombinant Fusion Proteins / physiology. Reverse Transcriptase Polymerase Chain Reaction. Sodium Hydroxide / toxicity. Transcription Factors. Transfection. Vascular Endothelial Growth Factor Receptor-2 / metabolism

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  • [ErratumIn] Invest Ophthalmol Vis Sci. 2007 Nov;48(11):4900
  • (PMID = 17065489.001).
  • [ISSN] 0146-0404
  • [Journal-full-title] Investigative ophthalmology & visual science
  • [ISO-abbreviation] Invest. Ophthalmol. Vis. Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA-Binding Proteins; 0 / KDEL receptor; 0 / Nuclear Proteins; 0 / Receptors, Peptide; 0 / Recombinant Fusion Proteins; 0 / Transcription Factors; 0 / regulatory factor X transcription factors; 55X04QC32I / Sodium Hydroxide; EC 2.7.10.1 / FLT1 protein, human; EC 2.7.10.1 / Vascular Endothelial Growth Factor Receptor-1; EC 2.7.10.1 / Vascular Endothelial Growth Factor Receptor-2; EC 3.4.22.- / Caspase 12; EC 3.4.22.- / Caspase 3
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13. Fujioka M, Sakamoto M, Azumi A, Kanomata N: [A case of conjunctival malignant melanoma treated with subconjunctival injection of interferon beta--efficacy and side effects]. Nippon Ganka Gakkai Zasshi; 2006 Jan;110(1):51-7
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  • [Title] [A case of conjunctival malignant melanoma treated with subconjunctival injection of interferon beta--efficacy and side effects].
  • BACKGROUND: The management of conjunctival malignant melanoma remains controversial.
  • Interferon-beta (IFN-beta) is a well-known antineoplastic agent against cutaneous malignant melanoma.
  • CASE: A 44-year-old man was referred to Kobe University, Hospital for treatment of pigmented lesions in the corneal limbus of his right eye, first recognized in 2000 and growing gradually.
  • Primary acquired melanosis (PAM) extended widely over the bulbar conjunctiva and the corneal surface.
  • These findings led to the clinical diagnosis of conjunctival malignant melanoma.
  • COURSE: The melanotic lesions were resected and histopathologically malignant melanoma was diagnosed.
  • Melanoma recurred a half-year later at 3 o'clock in the limbus of the right eye.
  • IFN-beta (3 million units/) was injected subconjunctivally 22 times.
  • Side effects observed were as follows: corneal epithelial erosion, increase of the corneal thickness, lid swelling, conjunctival congestion, subconjunctival hemorrhage, and liver dysfunction.
  • Melanotic lesions, including PAM, diminished 6 months after the end of treatment.
  • CONCLUSION: This therapeutic trial of local therapy using the subconjunctival administration of IFN-beta demonstrated excellent efficacy for the treatment of conjunctival malignant melanoma.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Conjunctival Neoplasms / drug therapy. Interferon-beta / administration & dosage. Melanoma / drug therapy

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  • (PMID = 16491874.001).
  • [ISSN] 0029-0203
  • [Journal-full-title] Nippon Ganka Gakkai zasshi
  • [ISO-abbreviation] Nippon Ganka Gakkai Zasshi
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 77238-31-4 / Interferon-beta
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14. Abraham LM, Selva D, Casson R, Leibovitch I: Mitomycin: clinical applications in ophthalmic practice. Drugs; 2006;66(3):321-40
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  • The drug is a bioreductive alkylating agent that undergoes metabolic reductive activation, and has various oxygen tension-dependent cytotoxic effects on cells, including the cross-linking of DNA.
  • It is widely used systemically for the treatment of malignancies, and has gained popularity as topical adjunctive therapy in ocular and adnexal surgery over the past 2 decades.
  • Hence, it has been used as adjunctive therapy in various ocular surgeries, such as glaucoma filtering surgeries, dacryocystorhinostomy, corneal refractive surgery and surgeries for ocular cicatrisation.
  • In addition, it has been used as an adjunct in the surgical management of pterygia, ocular surface squamous neoplasia, primary acquired melanosis with atypia and conjunctival melanoma.
  • [MeSH-major] Antibiotics, Antineoplastic / therapeutic use. Cicatrix / prevention & control. Conjunctival Neoplasms / drug therapy. Glaucoma / drug therapy. Melanoma / drug therapy. Mitomycin / therapeutic use. Neoplasms, Squamous Cell / drug therapy. Postoperative Complications / prevention & control
  • [MeSH-minor] Humans. Ophthalmology / trends. Randomized Controlled Trials as Topic. Trabeculectomy. Wound Healing / drug effects

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  • (PMID = 16526821.001).
  • [ISSN] 0012-6667
  • [Journal-full-title] Drugs
  • [ISO-abbreviation] Drugs
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] New Zealand
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 50SG953SK6 / Mitomycin
  • [Number-of-references] 172
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15. Jain V, Dabir S, Shome D, Dadu T, Natarajan S: Aspergillus iris granuloma: a case report with review of literature. Surv Ophthalmol; 2009 Mar-Apr;54(2):286-91
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Differential diagnoses of a fungal granuloma, a medulloepithelioma, and an amelanotic melanoma were considered.
  • An excisional biopsy of the mass was performed through a superior clear corneal incision.
  • Definitive differentiation of this rare entity from a foreign body, amelanotic melanoma, and other inflammatory conditions such as sarcoidosis and tuberculosis, may be possible only on microbiological and histo-pathological evaluation.
  • [MeSH-minor] Adult. Antifungal Agents / therapeutic use. Aqueous Humor / microbiology. Atropine / therapeutic use. Aza Compounds / therapeutic use. DNA, Fungal / analysis. Drug Therapy, Combination. Fluoroquinolones. Genome, Fungal / genetics. Humans. Male. Natamycin / therapeutic use. Polymerase Chain Reaction. Quinolines / therapeutic use

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  • (PMID = 19298905.001).
  • [ISSN] 0039-6257
  • [Journal-full-title] Survey of ophthalmology
  • [ISO-abbreviation] Surv Ophthalmol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Aza Compounds; 0 / DNA, Fungal; 0 / Fluoroquinolones; 0 / Quinolines; 7C0697DR9I / Atropine; 8O0C852CPO / Natamycin; U188XYD42P / moxifloxacin
  • [Number-of-references] 18
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16. Ambrus JL, Toumbis CA, Karakousis CP, Kulaylat M, Akhter S, Plavsic L: Study of antiangiogenic agents with possible therapeutic applications in neoplastic disorders and macular degeneration. J Med; 2000;31(5-6):278-82
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Study of antiangiogenic agents with possible therapeutic applications in neoplastic disorders and macular degeneration.
  • Using a previously developed method (Ambrus, et al., 1991), we found that pentoxifylline and thalidomide potentiate each others antiangiogenic effect induced by human malignant melanoma cells in the cornea of Macaca arctoides monkeys.
  • [MeSH-major] Angiogenesis Inhibitors / pharmacology. Cornea / drug effects. Corneal Neovascularization / drug therapy. Melanoma / pathology. Pentoxifylline / pharmacology. Thalidomide / pharmacology
  • [MeSH-minor] Animals. Cells, Cultured. Drug Combinations. Enzyme Inhibitors / pharmacology. Humans. Keratinocytes. Macaca. Macular Degeneration / drug therapy

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  • (PMID = 11508321.001).
  • [ISSN] 0025-7850
  • [Journal-full-title] Journal of medicine
  • [ISO-abbreviation] J Med
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Drug Combinations; 0 / Enzyme Inhibitors; 4Z8R6ORS6L / Thalidomide; SD6QCT3TSU / Pentoxifylline
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17. Scheinfeld N: A review of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops: possible uses and known side effects in cutaneous medicine. J Drugs Dermatol; 2007 Mar;6(3):352-5
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  • Recently, a number of medications approved for nondermatologic use have proved useful against dermatologic diseases.
  • Deferasirox--an oral iron chelator--could be an effective treatment against porphyria cutanea tarda, hemochromatosis, and pathogens such as mucor that thrive in iron rich environments.
  • Bortezomib, a proteasome inhibitor and multiple myeloma treatment, may be effective against nodular amyloid and has been effectively used against squamous cell carcinoma; although trials demonstrate it is ineffective against metastatic melanoma.
  • This article speculates that cyclosporine eye drops would also be useful for any disease causing ectropion or eclabion of the eye as well as toxic epidermal necrolysis-related eye pathology (in particular corneal scarring).
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Benzoates / therapeutic use. Boronic Acids / therapeutic use. Cyclosporine / therapeutic use. Iron Chelating Agents / therapeutic use. Protein Kinase Inhibitors / therapeutic use. Pyrazines / therapeutic use. Pyrimidines / therapeutic use. Skin Diseases / drug therapy. Skin Neoplasms / drug therapy. Thiazoles / therapeutic use. Triazoles / therapeutic use

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  • (PMID = 17373201.001).
  • [ISSN] 1545-9616
  • [Journal-full-title] Journal of drugs in dermatology : JDD
  • [ISO-abbreviation] J Drugs Dermatol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzoates; 0 / Boronic Acids; 0 / Iron Chelating Agents; 0 / Ophthalmic Solutions; 0 / Protein Kinase Inhibitors; 0 / Pyrazines; 0 / Pyrimidines; 0 / Thiazoles; 0 / Triazoles; 69G8BD63PP / Bortezomib; 83HN0GTJ6D / Cyclosporine; RBZ1571X5H / Dasatinib; V8G4MOF2V9 / deferasirox
  • [Number-of-references] 36
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18. Park MJ, Park IC, Bae IJ, Seo KM, Lee SH, Hong SI, Eun CK, Zhang W, Rhee CH: Tetraarsenic oxide, a novel orally administrable angiogenesis inhibitor. Int J Oncol; 2003 Jun;22(6):1271-6
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  • Orally administered tetraarsenic oxide (50 mg/kg/day) inhibited bFGF-induced new-vessel formation in a rat corneal micropocket assay, and reduced by about 54% the number of experimental pulmonary metastatic nodules in mice implanted with B16F10 melanoma cells.
  • [MeSH-major] Angiogenesis Inhibitors / pharmacology. Arsenates / pharmacology. Endothelium, Vascular / cytology. Lung Neoplasms / drug therapy. Neovascularization, Pathologic / prevention & control
  • [MeSH-minor] Administration, Oral. Animals. Capillaries. Cattle. Cell Cycle / drug effects. Cell Movement / drug effects. Cells, Cultured. Male. Mice. Mice, Inbred C57BL. Neoplasm Metastasis. Rats. Rats, Sprague-Dawley. Tumor Cells, Cultured

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  • (PMID = 12738993.001).
  • [ISSN] 1019-6439
  • [Journal-full-title] International journal of oncology
  • [ISO-abbreviation] Int. J. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Arsenates; 7631-89-2 / sodium arsenate
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19. Zhang G, Dass CR, Sumithran E, Di Girolamo N, Sun LQ, Khachigian LM: Effect of deoxyribozymes targeting c-Jun on solid tumor growth and angiogenesis in rodents. J Natl Cancer Inst; 2004 May 5;96(9):683-96
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  • METHODS: We used human microvascular endothelial cells (HMEC-1) transfected with a DNAzyme targeting the c-Jun mRNA (Dz13), related oligonucleotides, or vehicle in in vitro models of microvascular endothelial cell proliferation, migration, chemoinvasion, and tubule formation, a rat model of corneal neovascularization, and a mouse model of solid tumor growth and vascular endothelial growth factor (VEGF)-induced angiogenesis.
  • Dz13 blocked endothelial cell proliferation, migration, chemoinvasion, and tubule formation.
  • Dz13 inhibited VEGF-induced neovascularization in the rat cornea compared with vehicle control (Dz13 versus vehicle: 4.0 neovessels versus 30.7 neovessels, difference = 26.7 neovessels; P =.004; area occupied by new blood vessels for Dz13 versus vehicle: 0.35 mm2 versus 1.52 mm2, difference = 1.17 mm2; P =.005) as well as solid melanoma growth in mice (Dz13 versus vehicle at 14 days: 108 mm3 versus 283 mm3, difference = 175 mm3; P =.006) with greatly reduced vascular density (Dz13 versus vehicle: 30% versus 100%, difference = 70%; P<.001).
  • CONCLUSION: DNAzymes targeting c-Jun may have therapeutic potential as inhibitors of tumor angiogenesis and growth.
  • [MeSH-major] Angiogenesis Inhibitors / pharmacology. Antineoplastic Agents / pharmacology. DNA, Catalytic / pharmacology. Genes, jun. Melanoma, Experimental / drug therapy. Neovascularization, Pathologic / drug therapy. Proto-Oncogene Proteins c-jun / drug effects
  • [MeSH-minor] Animals. Blotting, Western. Cell Division. Cell Line. Cell Movement. Cornea / blood supply. Electrophoresis, Polyacrylamide Gel. Endothelial Cells. Female. Gene Expression Regulation, Neoplastic / drug effects. Humans. Male. Matrix Metalloproteinase 2 / metabolism. Matrix Metalloproteinase Inhibitors. Mice. Mice, Inbred C57BL. Rats. Rats, Sprague-Dawley. Reverse Transcriptase Polymerase Chain Reaction. Transfection. Vascular Endothelial Growth Factor A

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  • [CommentIn] J Natl Cancer Inst. 2004 May 5;96(9):644 [15126593.001]
  • (PMID = 15126605.001).
  • [ISSN] 1460-2105
  • [Journal-full-title] Journal of the National Cancer Institute
  • [ISO-abbreviation] J. Natl. Cancer Inst.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Antineoplastic Agents; 0 / DNA, Catalytic; 0 / Dz13 DNAzyme; 0 / Matrix Metalloproteinase Inhibitors; 0 / Proto-Oncogene Proteins c-jun; 0 / Vascular Endothelial Growth Factor A; EC 3.4.24.24 / Matrix Metalloproteinase 2
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20. Rudkin AK, Muecke JS: Topical mitomycin following cryotherapy for treatment of recurrent ocular surface melanoma. Can J Ophthalmol; 2009 Oct;44(5):e41
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Topical mitomycin following cryotherapy for treatment of recurrent ocular surface melanoma.

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  • (PMID = 19798814.001).
  • [ISSN] 1715-3360
  • [Journal-full-title] Canadian journal of ophthalmology. Journal canadien d'ophtalmologie
  • [ISO-abbreviation] Can. J. Ophthalmol.
  • [Language] ENG
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 50SG953SK6 / Mitomycin
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