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1.
Eur J Cancer Prev ; 14(4): 351-6, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16030425

ABSTRACT

Rhabdomysarcoma is the most common soft tissue tumour in children under the age of 15. Although the introduction of multimodal treatment programmes, including chemotherapy, radiation therapy and excision have increased the overall survival, the chemotherapeutic agents currently used for the treatment of rhabdomyosarcoma exhibit considerable toxicity. The aim of this study was to investigate the effects and possible mechanism(s) of action of resveratrol on human embryonal rhabdomyosarcoma (RD) cells. Resveratrol is a natural polyphenolic compound produced in a number of edible plants and has received considerable attention as a potential chemopreventive and/or chemotherapeutic agent against various types of cancers. In the present study, resveratrol was shown to inhibit cell proliferation of RD cells in a dose-dependent manner with an IC50 of 48.1 micromol/l and induce an arrest in the S/G2 phase of the cell cycle. As evident from immunocytochemical data, resveratrol treatment increased the size of the RD cells. Furthermore, resveratrol treatment resulted in a significant downregulation of cyclin B expression as demonstrated by western blot analyses. In conclusion, the present study shows that resveratrol exerts a strong inhibition of rhabdomyosarcoma cell proliferation in part by arresting cells in S/G2 phase of the cell cycle. These findings warrant further investigation to establish potential use of resveratrol as a relatively non-toxic chemotherapeutic agent for the treatment of rhabdomyosarcoma.


Subject(s)
Anticarcinogenic Agents/pharmacology , Cell Proliferation/drug effects , Stilbenes/pharmacology , Tumor Cells, Cultured/drug effects , Biopsy, Needle , Blotting, Western , Cell Cycle/drug effects , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Immunohistochemistry , Resveratrol , Rhabdomyosarcoma/drug therapy , Rhabdomyosarcoma/pathology , Risk Factors , Sensitivity and Specificity , Tumor Cells, Cultured/cytology
2.
Metabolism ; 49(11): 1440-3, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11092508

ABSTRACT

Individuals who are homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C --> T mutation have depressed serum folate (SF) and elevated plasma total homocysteine (tHcy) concentrations, which may affect folate requirements and increase the risk for coronary artery disease. A controlled metabolic study (14 weeks) using a depletion/repletion protocol was performed in women (aged 60 to 85 years, N = 33) to provide age-specific data on the effects of the MTHFR mutation on SF and tHcy status. Subjects consumed a moderately folate-deplete diet (118 microg/d) for 7 weeks, followed by 7 weeks of folate repletion with 200 or 415 microg/d provided as two different treatments. Following folate depletion, the mean SF concentration was lower for homozygous (P = .017) versus heterozygous subjects. Homozygotes for the 677C --> T mutation showed a higher (P = .015) percent increase in plasma tHcy (44%) than heterozygous (20%) or normal (15%) subjects. At week 7, the mean plasma tHcy concentration was higher in homozygous subjects (12.5 +/- 5.3 micromol/L, mean +/- SD) versus the heterozygous (10.8 +/- 3.8 micromol/L, P = .008) or normal (11.3 +/- 2.7 micromol/L, P = .001) genotype groups. Following folate repletion, plasma tHcy concentrations were not different between genotype groups, despite a higher (P < .016) SF concentration in subjects with the homozygous genotype. These data suggest that older women who are homozygous for the MTHFR 677C --> T mutation may be at risk for greater elevations in plasma tHcy in response to moderately low folate intake as compared with individuals with the normal or heterozygous genotypes.


Subject(s)
Folic Acid/administration & dosage , Homocysteine/blood , Mutation , Oxidoreductases Acting on CH-NH Group Donors/genetics , Aged , Aged, 80 and over , Female , Genotype , Humans , Methylenetetrahydrofolate Reductase (NADPH2)
3.
Am J Clin Nutr ; 72(1): 154-8, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10871574

ABSTRACT

BACKGROUND: The risk of neural tube defects (NTDs) is significantly reduced by supplemental folic acid. NTD risk may be associated with impaired absorption of polyglutamyl folate, the primary form of naturally occurring food folate, and of folic acid in supplements or fortified food. Stable-isotope methods provide the specificity needed to test this hypothesis. OBJECTIVE: We determined whether women who had an NTD-affected pregnancy had a reduced ability compared with control women to absorb polyglutamyl folate relative to folic acid. DESIGN: Healthy, nonpregnant women with a history of an NTD-affected pregnancy (cases; n = 11) and control women (n = 11) were administered an oral dose containing a mixture of [(2)H]pteroylpentaglutamate ([(2)H(2)]PteGlu(5); 233 nmol) and [(13)C]pteroylmonoglutamate ([(13)C(5)]PteGlu(1); 567 nmol) after a 30-d saturation protocol (2 mg unlabeled folic acid/d). Relative extents of absorption were evaluated by urinary excretion of (2)H(2)- and (13)C(5)-labeled folates 48 h postdose. RESULTS: During the first 24 h postdose, cases excreted less (f1.gif" BORDER="0"> +/- SD) [(2)H(2)]PteGlu(5) (21 +/- 12% compared with 37 +/- 19%; P = 0.01) and [(13)C(5)]PteGlu(1) (17 +/- 8% compared with 31 +/- 14%; P = 0.007) than did controls. No significant differences between cases and controls were detected in the percentage of [(2)H(2)]PteGlu(5) or [(13)C(5)]PteGlu(1) excreted during the second 24 h postdose or when the data were averaged over 48 h. However, excretion of the [(2)H(2)]folates tended to be lower in cases than in controls over the 48-h period (33 +/- 13% compared with 45 +/- 26%; P = 0.21). A similar trend (P = 0.29) for lower excretion of [(13)C(5)]folates in cases was also observed (31 +/- 16% compared with 39 +/- 17%). The ratio of urinary [(2)H(2)]folates to [(13)C(5)]folates did not differ significantly between cases and controls. CONCLUSION: These data suggest the need for a larger-scale study using stable-isotope methods to further investigate this hypothesis.


Subject(s)
Folic Acid/pharmacokinetics , Intestinal Absorption/physiology , Neural Tube Defects/prevention & control , Administration, Oral , Adult , Carbon Isotopes , Case-Control Studies , Female , Folic Acid/administration & dosage , Folic Acid/blood , Humans , Pteroylpolyglutamic Acids/pharmacokinetics , Pteroylpolyglutamic Acids/urine
4.
Eur J Cancer ; 36(6): 796-802, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10762754

ABSTRACT

The present study was undertaken to determine if (a) genistein induces topo II-mediated DNA damage in HT-29 colon cancer cells; and (b) if this damage is required to induce apoptosis. DNA damage was evaluated using the comet assay. Apoptosis was determined by the ethidium bromide/acridine orange staining technique. DNA breakage was noted within 1 h of treatment. Apoptosis was only induced with high concentrations (>/=60 microM) of genistein. Marked inhibition of HT-29 cell growth was evident at concentrations ranging from 60 to 150 microM. This was associated with a cell cycle arrest at G(2)/M. Similar findings were obtained in SW-620 and SW-1116 colon cancer cell lines. Aclarubicin, a topo II antagonist, reduced genistein-induced DNA breaks but did not reduce apoptosis. These data suggest that, in colon cancer cells, topo II serves as the enzymatic target of genistein. Furthermore, topo II-mediated DNA cleavage is not required for the induction of apoptosis.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Colonic Neoplasms/pathology , DNA Damage , Genistein/pharmacology , Aclarubicin/pharmacology , Antibiotics, Antineoplastic/pharmacology , Apoptosis/genetics , Cell Cycle/drug effects , Cell Division/drug effects , Colonic Neoplasms/genetics , DNA Topoisomerases, Type II/drug effects , DNA Topoisomerases, Type II/physiology , DNA, Neoplasm/drug effects , Dose-Response Relationship, Drug , Growth Inhibitors/pharmacology , Humans , Tumor Cells, Cultured
5.
Clin Plast Surg ; 25(3): 451-65, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9696905

ABSTRACT

Through deeper understanding of the physiology of wound healing and physico-chemical principles of scarring, biomedical science facilitates the development of new strategies in treatment and prevention of problem scars. It is important for practicing physicians and surgeons to be better aware of the full range of available techniques to control scar formation, and for any medical intervention to be planned in such a way that potential problems are apprehended and minimized or avoided. This article describes the clinical applications of recent research in scar control in order to provide such guidance.


Subject(s)
Cicatrix/therapy , Cicatrix, Hypertrophic/pathology , Humans , Wound Healing/physiology
6.
Obstet Gynecol ; 92(2): 167-70, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9699744

ABSTRACT

OBJECTIVE: To assess the effects of folate intake and pregnancy on plasma total homocyst(e)ine concentrations in women during the second trimester of pregnancy compared with young, healthy nonpregnant women. METHODS: The diet provided either 450 or 850 microg of folate per day. These levels are approximately the current (400 microg/day) and previous (800 microg/day) Recommended Dietary Allowances for folate in pregnant women. Folate was provided as both food folate (120 microg/day) and supplemental folic acid (either 330 or 730 microg/day) for a period of 12 weeks. Plasma homocyst(e)ine (sum of free and protein-bound homocysteine), serum folate, and erythrocyte folate concentrations were determined weekly. RESULTS: Homocyst(e)ine concentrations were lower in pregnant women during the second trimester of normal pregnancy than in nonpregnant controls, independent of dietary folate intake. The overall mean (+/- standard deviation) homocyst(e)ine concentration of the pregnant subjects (5.4 +/- 1.4 micromol/L) was significantly lower than that observed in the nonpregnant control group (8.7 +/- 1.7 micromol/L) (P < .0001). This difference in homocyst(e)ine concentrations remained constant throughout the 12 weeks of the investigation. CONCLUSION: The folate intakes in this investigation were adequate to maintain constant homocyst(e)ine concentrations in pregnant and nonpregnant women. The lower homocyst(e)ine concentrations observed in pregnant subjects compared with nonpregnant controls may be a physiologic response to pregnancy.


Subject(s)
Folic Acid/pharmacology , Homocysteine/blood , Homocysteine/drug effects , Adolescent , Adult , Female , Humans , Pregnancy , Pregnancy Trimester, Second
7.
Br J Cancer ; 77(9): 1395-404, 1998 May.
Article in English | MEDLINE | ID: mdl-9652754

ABSTRACT

We hypothesized that unexplained increases in nucleoside triphosphates (NTP) observed by 31P magnetic resonance spectroscopy (MRS) after treatment of tumours by DNA-damaging agents were related to chemotherapy-induced up-regulation of the bcl-2 gene and DNA damage prevention and repair processes. To test this hypothesis, we treated HT-29 cells with 10(-4) M nitrogen mustard (HN2) and performed sequential perchloric acid extractions in replicate over 0-18 h. By reference to an internal standard (methylene diphosphonic acid), absolute changes in 31P-detectable high-energy phosphates in these extracts were determined and correlated with changes in bcl-2 protein levels, cell viability, cell cycle, apoptosis and total cellular glutathione (GSH) (an important defence against DNA damage from alkylating agents). After HN2 administration, bcl-2 protein levels in the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but apoptosis measured using fluorescence techniques remained in the 1-4% range. Increased cell division was noted at 4 h. Two high-energy interconvertible phosphates, NTP (P < or = 0.006) and phosphocreatine (PCr) (P < or = 0.0002), increased at 2 h concurrently with increased levels of bcl-2 protein and glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased NTP after chemotherapy.


Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Genes, bcl-2/drug effects , Glutathione/drug effects , Mechlorethamine/pharmacology , Phosphocreatine/metabolism , Purine Nucleotides/metabolism , Adenosine Triphosphate/metabolism , Ammonia/pharmacology , Apoptosis/drug effects , Cell Cycle/drug effects , Chromatography, High Pressure Liquid , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Cytidine Triphosphate/metabolism , Guanosine Triphosphate/metabolism , HT29 Cells/drug effects , Humans , Magnetic Resonance Spectroscopy , Up-Regulation , Uridine Triphosphate/metabolism
8.
Prenat Diagn ; 18(6): 545-55, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9664599

ABSTRACT

While folate supplementation reduces the risk of recurrent neural-tube defects (NTD), both folate and cobalamin deficiencies may be independent risk-factors for neural-tube defects. Folate-dependence and impaired remethylation of homocysteine are implicated as mechanisms for NTD. There are few references reported for folate, cobalamin, homocysteine and methionine in the fetal compartment. This case-controlled pilot study of amniotic fluid (AF) samples derived from 16 NTD pregnancies and 64 age-matched controls quantities total homocysteine (tHcy), total cysteine (tCys), folate, cobalamin (B12), and methionine. Only decreased AF B12 concentrations were found (150 pg/ml versus 540 pg/ml, P < 0.02). Since cobalamin, folate and homocysteine participate in the remethylation of homocysteine, via methyl transfer from 5-methyltetrahydrofolate to B12, to methionine, we compared ratios of these methionine synthase (EC 2.1.1.13)-related intermediates. The ratio of B12/folate for NTD versus controls was 48 (34-90) versus 126 (123-182), P < 0.001. The ratio of methionine/(folate x tHcy) was 1.4 (1.2-2.2) versus 2.7 (2.4-3.3), P < 0.001. We conclude that AF from pregnancies with NTD have lower B12 concentrations, and that ratios of product to substrate(s) of homocysteine remethylation suggest impaired methionine synthase in the fetal compartment through the early second trimester.


Subject(s)
Amniotic Fluid/chemistry , Neural Tube Defects/metabolism , Vitamin B 12/analysis , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/metabolism , Amniocentesis , Case-Control Studies , Cysteine/analysis , Double-Blind Method , Female , Folic Acid/analysis , Homocysteine/analysis , Homocysteine/metabolism , Humans , Methionine/analysis , Methylation , Pilot Projects , Pregnancy , Reference Values
9.
Metabolism ; 47(2): 207-11, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9472972

ABSTRACT

Elevated total plasma homocysteine (tHcy) is recognized as an independent risk factor for occlusive vascular disease. However, it is not known how much of the observed hyperhomocysteinemia in patients with vascular disease is due to heterozygosity for cystathionine-beta-synthase (CbetaS) deficiency, because a clinically useful screening method is unavailable. To determine this, parents of children who are homozygous for CbetaS deficiency (affected with homocystinuria) and a control population were compared for tHcy, total plasma cysteine (tCys), plasma folate, and plasma vitamin B12. The group of obligate heterozygotes had increased tHcy (P < or = .01), decreased tCys (P < or = .01), and decreased plasma folate (P < or = .01). The calculated ratios of tHcy/tCys (P = .01) and tHcy/plasma folate (P = .003) were the best metabolic discriminants for genotype. These ratios are likely to prove useful in heterozygote screening for CPS deficiency and in the development of rational treatment strategies for patients with increased tHcy.


Subject(s)
Cystathionine beta-Synthase/deficiency , Cysteine/blood , Folic Acid/blood , Genetic Carrier Screening , Homocysteine/blood , Homocystinuria/genetics , Adult , Aged , Female , Humans , Male , Middle Aged , Vitamin B 12/blood
10.
Arch Surg ; 131(4): 424-9, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8615730

ABSTRACT

OBJECTIVES: To determine whether economically disadvantaged urban women with locally advanced breast cancer (American Joint Committee on Cancer stages IIB to IIIB) have rates of response to sequential neoadjuvant chemotherapy and radiation, breast salvage rates, overall survival rates, and disease-free survival rates comparable with those previously reported in other socioeconomic groups and to compare these variables in different ethnic groups within the study population. DESIGN: Prospective, nonrandomized, case series. SETTING: Urban county hospital. PATIENTS: Thirty-seven women with locally advanced breast cancer who came to the breast clinic at Cook County Hospital, Chicago, Ill, during a 3-year interval. INTERVENTION: Sequential chemoradiation followed by surgery in selected patients. MAIN OUTCOME MEASURES: Comparison of clinical response rates, disease-free survival rates, and breast salvage rates between different ethnic groups in the study population. RESULTS: In the entire group, the overall response rate to neoadjuvant chemotherapy was 73%, with a complete response rate of 32%. Twenty-five percent of patients whose tumors responded incompletely to chemotherapy had a complete response after subsequent radiation. With a mean follow-up of 18.7 months, 65% of patients had no evidence of disease, and breast salvage without evidence of recurrent disease was achieved in 38% of patients. No differences in overall response rates, breast salvage rates, or early disease-free survival rates were observed within different ethnic groups in the study population, and these results are generally comparable with previously reported results in other socioeconomic groups. CONCLUSION: These results do not show significant differences in responses to sequential chemotherapy and irradiation, in breast salvage rates, or in survival between different ethnic groups in this study population.


Subject(s)
Breast Neoplasms/therapy , Poverty , Urban Population , Black or African American , Breast Neoplasms/ethnology , Breast Neoplasms/mortality , Combined Modality Therapy , Disease-Free Survival , Female , Hispanic or Latino , Humans , Illinois/epidemiology , Neoplasm Staging , Survival Rate , White People
12.
Int Surg ; 79(1): 6-10, 1994.
Article in English | MEDLINE | ID: mdl-8063557

ABSTRACT

Lymphadenectomy has an acknowledged role in the staging of most solid tumors, however, its therapeutic role remains controversial. To date, several prospective, randomized, controlled trials comparing either extended vs. conventional lymphadenectomy (in breast cancer) or prophylactic lymphadenectomy vs observation (in N0 patients with breast cancer or melanoma) have failed to show survival differences between treatment arms. Gastrointestinal cancers, including gastric cancer, represent a special case of this general problem in that intra-abdominal nodes are not clinically accessible and accurate radiographic determination of nodal involvement continues to be problematic. Without question, staging and technical considerations dictate removal of at least some perigastric lymph nodes. However, the one prospective study testing survival benefit for R2 vs R1 lymphadenectomy in gastric cancer was negative. This study suffers from small sample size compounded by post operative pathologic upstaging resulting in entry of a moderate percentage of ineligible patients. Japanese surgeons have also been generally critical of the extent of R2 dissections in Western surgical studies. A second prospective trial, presently underway, addresses these concerns as well as other concerns about selection bias in older retrospective studies and should finally resolve the issue of the therapeutic efficacy of extensive lymphadenectomy in gastric cancer.


Subject(s)
Lymph Node Excision , Lymphatic Metastasis , Stomach Neoplasms/surgery , Clinical Trials as Topic , Humans , Stomach Neoplasms/pathology
14.
Surgery ; 112(4): 689-93, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1411939

ABSTRACT

BACKGROUND: This study examines the potential impact of intercurrent diseases on survival after adjuvant chemotherapy for node-negative (N0) breast cancer in light of 30-year follow-up results in 136 patients with N0 disease receiving only regional therapy at the University of Texas M.D. Anderson Cancer Center between 1958 and 1960. METHODS: We made a retrospective review of treatment records. RESULTS: Thirty-nine women (28.6%) died of the initial breast cancer, including 12 (22%) of 54 premenopausal women, 15 (43%) of 35 perimenopausal women, and 12 (25%) of 47 postmenopausal women (p less than or equal to 0.09). Six (12%) of 49 patients with T1 disease died of the initial breast cancer versus 27 (38%) of 70 patients with T2 disease and 6 (35%) of 17 patients with T3 disease (p less than or equal to 0.006). Five of 10 women died of metachronous contralateral breast primary lesions. Deaths from other cancers occurred in 11%, 2.8%, and 6.4% of premenopausal, perimenopausal, and postmenopausal women, respectively. Deaths from nonmalignant conditions occurred in 22%, 20%, and 59% of premenopausal, perimenopausal, and postmenopausal women, respectively. Overall survival at 30 years was 35 (26%) of 136 patients. CONCLUSIONS: Given these statistics, if one postulates that adjuvant chemotherapy reduces the death rate from an initial breast cancer by 30% to 77% (estimates based on data from adjuvant chemotherapy trials in patients with N+ or N0 disease), a 5% to 12.9% increase in the 30-year survival would have resulted.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Mastectomy, Radical , Menopause , Middle Aged , Neoplasm Staging , Retrospective Studies , Survival Analysis , Time Factors
15.
Cancer ; 68(7): 1501-6, 1991 Oct 01.
Article in English | MEDLINE | ID: mdl-1893349

ABSTRACT

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Adenocarcinoma/secondary , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Etoposide/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Infusions, Intravenous , Lymphatic Metastasis , Male , Middle Aged , Stomach Neoplasms/mortality , Survival Analysis
16.
JAMA ; 263(16): 2216-20, 1990 Apr 25.
Article in English | MEDLINE | ID: mdl-2181162

ABSTRACT

Hyperbaric oxygen therapy involves intermittent inhalation of 100% oxygen under a pressure greater than 1 atm. Despite over a century of use in medical settings, hyperbaric oxygen remains a controversial therapy. The last 20 years have seen a clarification of the mechanism of action of hyperbaric therapy and a greater understanding of its potential benefit. However, despite the substantial evidence that hyperbaric oxygen may have a therapeutic effect in certain carefully defined disease states, many practitioners remain unaware of these findings or are concerned about using hyperbaric therapy because of the controversy it has engendered. This review examines the indications currently considered appropriate for hyperbaric oxygen and briefly evaluates animal and clinical data substantiating these indications. Areas in which the mechanism of action of hyperbaric oxygen is still not well understood, as well as possible new areas of applications, are discussed.


Subject(s)
Hyperbaric Oxygenation , Carbon Monoxide Poisoning/therapy , Clostridium Infections/therapy , Decompression Sickness/therapy , Embolism, Air/therapy , Humans , Hyperbaric Oxygenation/methods , Wound Healing
17.
Arch Surg ; 125(3): 317-21, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2306179

ABSTRACT

The therapeutic efficacy of isolated limb perfusion in patients with localized melanoma of the extremity remains controversial. We compared patients treated at the University of Texas M.D. Anderson Cancer Center, Houston, with wide local excision and isolated limb perfusion using either melphalan or imidazole carboxamide with a group matched for prognostic factors from the University of Alabama at Birmingham and the University of Sydney (Australia) who were treated with wide local excision alone. No significant difference in disease-free or overall survival rates was found between patients treated with wide local excision with adjuvant isolated limb perfusion or wide local excision alone. However, a subset of patients with thicker lesions (greater than 2.0 mm) treated with wide local excision and isolated limb perfusion using melphalan had a significant improvement in both disease-free and overall survival rates. These data suggest that isolated limb perfusion using melphalan may improve survival rates in selected patients with localized melanoma of the extremity who are at increased risk for local and regional micrometastases, and justifies the continued study of this treatment approach in prospective clinical trials.


Subject(s)
Chemotherapy, Cancer, Regional Perfusion , Melanoma/therapy , Skin Neoplasms/therapy , Aminoimidazole Carboxamide/administration & dosage , Aminoimidazole Carboxamide/analogs & derivatives , Antineoplastic Agents/administration & dosage , Arm/surgery , Chemotherapy, Cancer, Regional Perfusion/adverse effects , Chemotherapy, Cancer, Regional Perfusion/methods , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Humans , Leg/surgery , Lymphatic Metastasis , Melanoma/complications , Melanoma/mortality , Melphalan/administration & dosage , Middle Aged , Prognosis , Skin Neoplasms/complications , Skin Neoplasms/mortality , Survival Rate
19.
South Med J ; 82(8): 985-7, 989, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2762904

ABSTRACT

Isolated limb perfusion (ILP) for melanoma of the extremity was first used clinically more than 30 years ago. Although ILP with chemotherapeutic agents has become routine practice in many oncologic centers, few studies have evaluated the therapeutic efficacy of particular agents. Two consecutive groups of 100 patients with stage I extremity melanoma of 1.5 mm thickness or greater were treated by ILP with either melphalan (L-PAM) or dacarbazine (DTIC). Demographics, clinical and pathologic stage, disease site, and complications were similar in both groups. No significant difference in the overall incidence of recurrent disease at two years was found between patients treated with either DTIC or L-PAM (22% vs 16%, respectively; P = .28). Patients who had perfusion with L-PAM, however, had a lower incidence of in-transit metastasis and recurrence at the scar than those having DTIC therapy (4% vs 12%, P = .06) at two years of follow-up. This preliminary report suggests that L-PAM may be more effective than DTIC in controlling scar recurrences and in-transit metastasis. Continued follow-up of this series of patients, with further analysis of patterns of recurrence and disease-free and overall survival at five years, will be necessary to better define the relative efficacy of L-PAM and DTIC in isolated limb perfusion.


Subject(s)
Chemotherapy, Cancer, Regional Perfusion/methods , Dacarbazine/administration & dosage , Extremities , Melanoma/drug therapy , Melphalan/administration & dosage , Neoplasm Recurrence, Local/prevention & control , Adult , Cicatrix/prevention & control , Dacarbazine/therapeutic use , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Melanoma/mortality , Melanoma/pathology , Melphalan/therapeutic use , Middle Aged , Neoplasm Staging , Retrospective Studies
20.
Am J Surg ; 157(6): 595-606, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2658642

ABSTRACT

The overall cure rate for gastric cancer has changed relatively little in the United States over the past 30 years, largely because patients continue to present for treatment in advanced stages. The paucity of symptoms in early gastric cancer, the low incidence in the general United States population, and the lack of cost-effective screening methods suggest that improvements in early detection are unlikely. Hope for improved survival in late stage cases lies mostly in a better understanding of the pathophysiology and patterns of spread, in evolving techniques for more accurate perioperative staging, and in the gradually improving results of multimodality therapy for local-regional and systemic disease. A proposal is made for a new staging system integrating newer approaches to staging and for controlled trials of multimodality therapy in patients unlikely to be cured by surgery alone.


Subject(s)
Stomach Neoplasms , Algorithms , Combined Modality Therapy , Humans , Neoplasm Staging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/therapy
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