Mean Tumor Weight Research Articles

Schedule Dependent Efficacy of Gefitinib and Docetaxel for Bladder Cancer

We determined the sequence specific efficacy of gefitinib and docetaxel treatment for bladder cancer. This combination was selected because it is currently under study in a phase II clinical trial. In vitro antiproliferative effects of gefitinib, docetaxel and a combination were determined in the 4 bladder cancer cell lines 253J B-V, UM-UC-3, KU-7 and UM-UC-13 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle analysis was analyzed using flow cytometry and propidium iodide labeling. Epidermal growth factor receptor downstream signaling was assessed by Western blot analysis. In vivo nude mice were injected subcutaneously with 253J B-V cells and treated with placebo, gefitinib, docetaxel, docetaxel followed by gefitinib or gefitinib followed by docetaxel. Tumor kinetics were established. Gefitinib demonstrated antiproliferative effect against 253J B-V cells (50% inhibitory concentration less than 0.5 muM) but no apoptotic effect in vitro, whereas docetaxel demonstrated antiproliferative and apoptotic effects. When gefitinib and docetaxel were combined, gefitinib enhanced the apoptotic and antiproliferative effects of docetaxel only when gefitinib was administered following docetaxel pretreatment. Apoptosis increased from 45% to 66%. In vivo there were significant differences in tumor weight in mice treated with combination therapy vs gefitinib or docetaxel alone. Importantly improved efficacy was observed when docetaxel was followed by gefitinib administration compared with gefitinib followed by docetaxel (mean tumor weight 42 vs 93 mg, p = 0.022). Sequence specific efficacy was not observed in UM-UC-3, UM-UC-13 and KU-7 cells, which are resistant to gefitinib. Docetaxel followed by gefitinib demonstrated sequence specific efficacy against gefitinib sensitive bladder cancer compared with gefitinib followed by docetaxel or either drug alone. Accordingly gefitinib administration concurrently or after chemotherapy might be the sequence of choice and it should be considered for future clinical trials.

Preparation and Stability of N-Terminal Mono-PEGylated Recombinant Human Endostatin

Endostatin can specifically inhibit endothelial proliferation and potently inhibit angiogenesis and tumor growth. N-Terminal site-specific mono-PEGylation of recombinant human endostatin (mPEG-rhES) was accomplished by using methoxy poly-ethylene glycol (mPEG) propionaldehyde with an average molecular weight of 5000 Da through a reactive terminal aldehyde group. The site-specific mPEG conjugation was conducted under optimal conditions, which were identified through a statistical L(9)(3(4)) orthogonal test. In this study, we have investigated the stability and antitumor activity of mPEG-rhES. SDS-PAGE, RP-HPLC, and UV spectrophotometric analysis were used to identify the purity and stability of mPEG-rhES. When incubated with protease or placed in an extreme environment, mPEG-rhES was more stable than rhES. The unmodified and PEGylated rhES were tested for their ability to inhibit the tumor growth of mouse H22 liver cancer in male mice. In a multiple versus single doses comparison study, daily administration of 0.25, 0.50, and 1.00 micromol/kg of unmodified rhES for 7 days resulted in 26.9%, 43.0%, and 64.9% reductions in tumor weight, respectively, while single doses of 0.13, 0.25, and 0.50 micromol/kg of the PEGylated protein per day resulted in 24.8%, 38.0%, and 64.5% reductions, respectively. Both treatments resulted in statistically significant reductions in mean tumor weight as compared to the physiological saline solution (control)-treated mice, with the dose of mPEG-rhES being a half of rhES, respectively, while the tumor inhibition rates were similar. Therefore, it is suggested that PEGylation enhances the stability of rhES and improves its antitumor activity.

Antitumor effect of combination of S-1 and docetaxel on the human breast cancer xenograft transplanted into SCID mice

In vivo experiments were performed on breast cancer xenografts to examine whether the combination therapy with S-1, an oral dihydrouracil dehydrogenase (DPD) inhibitory fluoropyrimidine, plus docetaxel functions as an additive/synergistic modulator in tumor growth. The human breast cancer xenograft, MDA-MB-435SHM, was inoculated into SCID female mice. The tumor growth and thymidylate synthase (TS)/DPD activity of tumors treated with the agents were investigated. The T/C value (relative mean tumor weight of the treated group/relative tumor weight of the control group) of the group treated with docetaxel, S-1 and combination therapy were 45.3, 63.1 and 29.8%, respectively; suggesting the positive antitumor effects of the combination therapy in particular. In addition, significant down-regulation of DPD activity was also observed in the tumors treated with S-1, docetaxel and their combination. Down-regulation of the DPD activity of the tumors is also considered to be correlated with the antitumor effect of the treated groups, suggesting its influence on the synergistic effect of the combination therapy.

Effects and mechanisms of endostatin on the growth of ovarian cancer SKOV3 cells in vitro and in vivo

To evaluate the inhibitory effect of Endostatin on ovarian cancer cell line SKOV3 and to investigate the possible mechanism of the inhibition. Using MTT, transmission electron microscope (TEM) and immunocytochemistry, the effects of Endostatin on the proliferation of SKOV3 cells were studied. Nude mice were subcutaneously implanted with SKOV3 cells. The cell apoptosis of implanted tumor was detected by TUNEL and TEM. The expressions of bcl-2 and bax in implanted tumor tissues were measured by RT-PCR and immunohistochemistry. Endostatin significantly inhibited the proliferation of SKOV3 cells in vitro (P<0.01) and induced cell apoptosis, whereas the expressions of bcl-2 and bax were not changed obviously in SKOV3 cell treated with Endostatin. The mean tumor weight of Endostatin treated group was markedly lower than that of PBS control group (P<0.05). The expression of bcl-2 was down-regulated in Endostatin treated group, but bax was not influenced. The results demonstrated that Endostatin might have anti-tumor effect on ovarian carcinoma. One of the important mechanisms of Endostatin effect of anti-angiogenic and anti-tumor activities might involve regulating the bcl-2/bax expression and inducing apoptosis.

Indian Primary Hyperparathyroidism Patients with Parathyroid Carcinoma do not Differ in Clinicoinvestigative Characteristics from Those with Benign Parathyroid Pathology

No foolproof preoperative diagnostic indicators of parathyroid carcinoma (PC) exist in absence of nonskeletal metastases. Palpable parathyroid tumor, advanced skeletal and renal manifestations, and very high serum calcium and parathyroid hormone levels are considered strong predictors. Most of these features are common in Indian primary hyperparathyroidism (PHPT) patients although only few have PC. The aim of this study was to identify dependable clinicoinvestigative predictors of PC in Indian PHPT patients. Clinical, biochemical, radiological, and densitometric attributes of 100 PHPT patients who underwent successful parathyroidectomy (1990-2004) were studied. Various parameters of patient groups with parathyroid adenoma (n = 84), primary hyperplasia (n = 12), and carcinoma (n = 4) were compared using ANOVA, with P value < 0.05 considered significant. Mean age of patients was 37.4 years, with no difference in the 3 groups (P = 0.92). Patients in 3 groups had comparably severe bone disease; 36 had coexistent renal disease. Two patients with PC and 27 (32%) with adenoma had palpable parathyroid tumor. None of the biochemical parameters predicted malignant pathology. Mean tumor weight (milligram) in carcinoma patients (15,080 +/- 5,638.02) was significantly higher than those with adenoma (5,724 +/- 1,257.9) (P = 0.002). Postoperative course and recovery in carcinoma patients were similar to those with adenoma. In follow-up (mean: 33 months), none of the adenoma patients were found to have persistent/recurrent PHPT attributable to missed PC. Indian patients with parathyroid adenoma, hyperplasia, and carcinoma were not found to differ in their clinical, biochemical, and pathological characteristics except for significantly higher tumor weight in the carcinoma group.

Effective local control of prostate cancer by intratumoral injection of 166Ho-chitosan complex (DW-166HC) in rats

The aim of this study was to evaluate the therapeutic effect and morphological alterations resulting from (166)Ho-chitosan complex (DW-166HC) in an animal model of prostate cancer. First, in a subcutaneous tumor model, 80 rats were randomly divided into four groups (n=20 in each group), and intratumoral injections of 0.05 ml (normal saline in group 1,( 165)Ho-chitosan complex solution in group 2, DW-166HC solution (10 mCi) in group 3, and DW-166HC solution (20 mCi) in group 4) were performed when the tumor measured approximately 1 cm along its long axis in each group. Further, in an orthotopic tumor model, 40 rats were similarly randomly divided into four groups (n=10 in each group), and intraprostatic injections of 0.05 ml [PBS in group 1,( 165)Ho-chitosan complex solution in group 2, DW-166HC solution (0.5 mCi) in group 3 and DW-166HC solution (1 mCi) in group 4] were performed at 1 week after implantation of the AIT cell line in the ventral prostate. In the subcutaneous tumor model, mean tumor weights of groups 3 and 4 were significantly lower than those of groups 1 and 2 at 2 and 4 weeks post injection (p<0.05). At 2 and 4 weeks after injection in the orthotopic tumor model, the mean weights of the prostate, including tumor, in groups 3 and 4 were also significantly lower than those in groups 1 and 2 (p<0.05). No adverse injury was seen in adjacent organs at histopathologic examination. Intratumoral injection of the beta-emitting radionuclide (166)Ho as a form of complex solution with chitosan appears to be a promising alternative therapeutic modality for the local control of prostate cancer.

Combined low‐dose imatinib mesylate and paclitaxel lack synergy in an experimental model of extra‐osseous hormone‐refractory prostate cancer

To determine the efficacy of low-dose imatinib mesylate (STI571) alone or combined with a taxane (paclitaxel) in inhibiting the growth of experimental extra-osseous hormone-refractory prostate cancer. Orthotopic PC3 prostate tumours were established in male severe combined-immunodeficient mice; on day 3 the mice were randomly assigned to one of four groups: paclitaxel 10 mg/kg intraperitoneally once a week; STI571 50 mg/kg once a day for 6/7 weekdays; combined paclitaxel and STI571; and vehicle-treated controls. On day 40, the primary prostate tumour and metastatic lymphadenopathy were removed and measured. Effects were correlated with tumour cell proliferation and microvessel density. Paclitaxel reduced the mean tumour weight and volume by 21.3% (not significant) and 73.7% (P < 0.05), respectively, compared to controls, and reduced the number of lymph node metastases by 49.1% (P < 0.05) and mean lymph node size by 13.5% (not significant). Adding low-dose STI571 had a small additive effect on tumour weight and the incidence of lymph node metastases, but this was not significant compared to paclitaxel alone. STI571 alone did not inhibit tumour progression. Antitumour effects were associated with parallel changes in tumour cell proliferation with no significant changes in neo-angiogenesis. Combined low-dose STI571 and paclitaxel had little synergy in this experimental model. Low-dose STI571 monotherapy was not effective in extra-osseous disease, apparently due to a site-specific failure to up-regulate beta-platelet-derived growth factor receptor expression in prostate cancer cells and associated tumour stroma.

The study of inhibition effect of octreotide on the growth of hepatocellular carcinoma xenografts in situ in nude mice

To observe the effect of octreotide (OCT) on inhibiting hepatocellular carcinoma (HCC) and investigate its mechanisms. Nude mice bearing xenografts in situ were treated with OCT or saline control for 7 weeks since tumor implantation. The immunohistochemistry for somatostatin receptor 2 (SSTR2), cMet, transforming growth factor beta1 (TGFbeta1), phospho-Smad2, Smad4 and Smad7 was performed. SSTR2 and Smad4 mRNA expression was measured by semi-quantitative RT-PCR. After OCT treatment, the mean tumor weight in mice given OCT (0.17 +/- 0.14 g) was significantly lower than that of the control group (0.53 +/- 0.06 g). The inhibition rate of tumor was 67.9%. mRNA and protein expression of SSTR2, Smad4 in tumor cells of the treatment group were significantly more than that of the control group. cMet expression in OCT group was remarkably lower than that in control group. Between two groups, the expression of TGFbeta1, phospho-Smad2 and Smad7 were not remarkably different. In addition, phospho-Smad2 expression in HCC was significantly less than that of the normal hepatic cell. OCT can inhibit the growth of HCC xenografts markedly. The mechanisms of OCT-induced inhibition effect may be related to up-regulating SSTR2 expression, down-regulating cMet, and recovering the function of TGFbeta/Smads-induced antitumor. In addition, the decreased expression of phospho-Smad2 may be an important feature of Bel7402 cells.

Photodynamic Therapy of Human Undifferentiated Thyroid Carcinoma–Bearing Nude Mice Using Topical 5-Aminolevulinic Acid

We determined and evaluated the effect of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) cream in treating human undifferentiated thyroid carcinoma (UTC)-bearing nude mice. UTC constitutes almost 10% of thyroid cancers and shows a very poor response to chemotherapy. Today PDT with topical ALA is successfully used for the treatment of a variety of neoplastic and non-neoplastic diseases. UTC tumor was implanted in the right flank of the nude mice after anesthesia. When the actual tumor size reached about 345 mm3, all mice were divided randomly into a treatment group (n = 10) and a control group (n = 10). ALA cream was applied to tumors in treated mice and left on for 6 has a retention interval; then the tumors were irradiated by a 633-nm diode laser with an incident dose of 60 J/cm2. The tumor volumes were measured 7, 14, and 21 days after PDT in both groups. The percentage of tumor growth delay after PDT was calculated. All mice were sacrificed and the tumor weights were determined 21 days after PDT. Mean tumor volumes on 21 days after PDT were 1141.19 +/- 153.74 mm3 in the treated group and 2370.75 +/- 300.42 mm3 in the control group. The percentage of tumor growth delay was -48.13 +/- 13.76 7 days after PDT, -54.9 +/- 8.83 14 days after PDT, and -51.11 +/- 8.95 21 days after PDT. Mean tumor weights 21 days after PDT were 1.78 +/- 0.32 g in the treated group and 3.60 +/- 0.60 g in the control group. There were significant differences (p < 0.001) in mean tumor volume and weight between the treated and control groups after PDT. PDT is effective in delaying the growth of UTC-bearing nude mice using topical ALA cream and laser light with inappropriate parameters. ALA cream as a topically applied photosensitizer was effective, safe, and convenient in PDT.

Effects of meal timing on tumor progression in mice

Meal timing can reset circadian clocks in peripheral tissues. We investigated the effects of such non–photic entrainment on tumor growth rate. Two experiments involved a total of 61 male B6D2F 1 mice synchronized with an alternation of 12 h of light (L) and 12 h of darkness (D) (LD12:12). Mice were randomly allocated to have access to food ad libitum, or restricted to 4 or 6 h during L or D. Rest-activity and body temperature, two circadian outputs, were monitored with an intra-peritoneal sensor. Glasgow osteosarcoma was inoculated into both flanks of each mouse ten days after meal timing onset. Before tumor inoculation, meal timing during D amplified the 24-h rhythms in rest-activity and body temperature with minimal phase alteration as compared to ad libitum feeding. Conversely, meal timing during L induced dominant 12-h or 8-h rhythmic components in activity, nearly doubled the 24-h amplitude of body temperature and shifted its acrophase (time of maximum) from ∼mid-D to ∼mid-L. Thirteen days after tumor inoculation, mean tumor weight (± SEM, mg) was 1503 ± 150 in ad libitum mice, 1077 ± 157 in mice fed during D and 577 ± 139 in mice fed during L (ANOVA, p < 0.0001). Overall survival was prolonged in the mice fed during L (median, 17.5 days, d) as compared with those fed during D (14.5 d) or ad libitum (14 d) (Log Rank, p = 0.0035). The internal desynchronization produced by meal timing during L slowed down tumor progression, an effect possibly resulting from improved host-mediated tumor control and/or altered tumor circadian clocks.

A surgical approach to adrenocortical tumors in children: the mainstay of treatment

Background Adrenocortical tumors (ACTs) are rare in the pediatric population. The pathogenesis, prognostic indicators, and management of these tumors are still unclear because of its infrequent occurrence. This case series presents the surgical experience of the authors’ center over 29 years. Methods The medical records of children treated for ACTs between 1974 and 2003 were reviewed. Information on age, sex, presenting symptoms, hormonal levels, pathology, stage, treatment, and outcome was obtained. Results Nine children (5 girls, 4 boys) were treated for ACTs. The median age at presentation was 29 months (range, 5 months to 11 years). Endocrine dysfunction was found in 8 patients. Four presented with virilizing symptoms, 4 presented with both virilizing and Cushing’s symptoms, and 1 patient with Beckwith-Wiedemann syndrome was identified during routine screening. One was an adenoma, and 8 were carcinomas. Of the carcinomas, 3 were stage I, and 5 were stage II. The mean tumor weight was 125 g (range, 42 g to 336 g) with a mean volume of 139 cm 3 (range, 30 cm 3 to 626 cm 3). All patients had complete excision of the tumor with spillage occurring in 2 cases. Lymph node biopsies were done in all but 2 patients. Two patients were treated with chemotherapy because of large tumor size and nodal involvement. All patients are doing well including those with tumor spillage. Conclusions This study shows that surgical excision continues to be the mainstay of treatment for ACTs. Extensive lymph node biopsy in small ACTs can probably be avoided given the generally good outcome with surgery alone. The role of adjuvant chemotherapy remains unclear because most of the children in our series were effectively treated with surgical resection only. Patients should be enrolled in multicenter trials to assess the added value of chemotherapy.

Enhanced Growth of Pancreatic Tumors in SPARC-Null Mice Is Associated With Decreased Deposition of Extracellular Matrix and Reduced Tumor Cell Apoptosis

Abstract SPARC, a matricellular glycoprotein, modulates cellular interaction with the extracellular matrix (ECM). Tumor growth and metastasis occur in the context of the ECM, the levels and deposition of which are controlled in part by SPARC. Tumor-derived SPARC is reported to stimulate or retard tumor progression depending on the tumor type, whereas the function of host-derived SPARC in tumorigenesis has not been explored fully. To evaluate the function of endogenous SPARC, we have examined the growth of pancreatic tumors in SPARC-null (SP−/−) mice and their wild-type (SP+/+) counterparts. Mouse pancreatic adenocarcinoma cells injected s.c. grew significantly faster in SP−/− mice than cells injected into SP+/+ animals, with mean tumor weights at sacrifice of 0.415 ± 0.08 and 0.086 ± 0.03 g (P &amp;lt; 0.01), respectively. Lack of endogenous SPARC resulted in decreased collagen deposition and fiber formation, alterations in the distribution of tumor-infiltrating macrophages, and decreased tumor cell apoptosis. There was no difference in microvessel density of tumors from SP−/− or SP+/+ mice. However, tumors grown in SP−/− had a lower percentage of blood vessels that expressed smooth muscle α-actin, a marker of pericytes. These data reflect the importance of ECM deposition in regulating tumor growth and demonstrate that host-derived SPARC is a critical factor in the response of host tissue to tumorigenesis.

Limited tumor growth (HT29) in vivo under RO205-2349 is due to increased apoptosis and reduced cell volume but not to decreased proliferation rate

The peroxisome proliferator-activated receptor (PPARγ) is a nuclear receptor that plays a regulatory role in cell differentiation and proliferation. PPARγ was first detected in adipocytes, however, it has been shown that this receptor is also expressed in normal as well as tumor cells including malignant colonic epithelial cells. In this study, the effect of the PPARγ agonist RO205-2349, a recently developed thiazolidinedione, on tumor growth was evaluated. For this purpose, human colon cancer cells (HT29) were grown in severe combined immunodeficient mice. Under daily RO205-2349 treatment (50 mg/kg/day) a significantly reduced tumor weight became evident after 3 weeks. In the control ( n=10) and treatment ( n=10) groups the mean tumor weights were 0.45 and 0.16 g, respectively. The mean percentages of apoptotic cells were 0.8 and 2.7% in the control and treatment groups, respectively, and the cell diameter measured on average 11.4 and 9.4 μm. In contrast, cell proliferation and differentiation, which are considered to be influenced by the PPARγ, remained unaffected as could be seen by Ki-67 and carcinoembryonic antigen immunoreactivity indicating that increased rate of apoptosis and cell shrinkage are responsible for the differences in tumor growth. Hence, in this human/mouse xenograft model, mechanisms other than the classical activation of PPARγ are likely reasons causing limited tumor growth.

In vivo preservation of steroid specificity in CWR22 xenografts having a mutated androgen receptor.

In vitro studies of CWR22 tumor cells lack steroid specificity. We sought to determine if CWR22 xenografts also lack steroid specificity. We injected castrated nude mice with CWR22 tumor cells (6 x 10(6) cells) and implanted Alzet osmotic pumps that delivered approximately 1 mg steroid/kg body weight/day. Serum PSA levels were detectable in intact mice and castrated mice treated with testosterone (T), but not in those treated with estradiol (E(2)), progesterone (P), or flutamide (F). T maintained mean tumor weight similar to that in intact mice (P = NS). We observed no tumors in castrated mice or mice treated with E(2), P, or F, and tumor histology was consistent with weights. The mutation of the androgen receptor (H874Y) that occurs in the CWR22 xenograft model of human prostate cancer does not significantly affect in vivo steroid specificity for E(2), P, or F.

Mcl-1 Antisense Therapy Chemosensitizes Human Melanoma in a SCID Mouse Xenotransplantation Model

It is well established that high expression of the antiapoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL can significantly contribute to chemoresistance in a number of human malignancies. Much less is known about the role the more recently described Bcl-2 family member Mcl-1 might play in tumor biology and resistance to chemotherapy. Using an antisense strategy, we here address this issue in melanoma, a paradigm of a treatment-resistant malignancy. After in vitro proof of principle supporting an antisense mechanism of action with specific reduction of Mcl-1 protein as a consequence of nuclear uptake of the Mcl-1 antisense oligonucleotides employed, antisense and universal control oligonucleotides were administered systemically in combination with dacarbazine in a human melanoma SCID mouse xenotransplantation model. Dacarbazine, available now for more than three decades, still remains the most active single agent for treatment of advanced melanoma. Mcl-1 antisense oligonucleotides specifically reduced target protein expression as well as the apoptotic threshold of melanoma xenotransplants. Combined Mcl-1 antisense oligonucleotide plus dacarbazine treatment resulted in enhanced tumor cell apoptosis and led to a significantly reduced mean tumor weight (mean 0.16 g, 95% confidence interval 0.08-0.26) compared to the tumor weight in universal control oligonucleotide plus dacarbazine treated animals (mean 0.35 g, 95% confidence interval 0.2-0.44) or saline plus dacarbazine treated animals (mean 0.39 g, 95% confidence interval 0.25-0.53). We thus show that Mcl-1 is an important factor contributing to the chemoresistance of human melanoma in vivo. Antisense therapy against the Mcl-1 gene product, possibly in combination with antisense strategies targeting other antiapoptotic Bcl-2 family members, appears to be a rational and promising approach to help overcome treatment resistance of malignant melanoma.

Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium–derived factor in a xenograft model

Background/Purpose: Pigment epithelium–derived factor (PEDF), a potent endogenous inhibitor of angiogenesis, is highly expressed in the kidney. The authors postulated that systemic administration of PEDF would decrease Wilms' tumor growth in a xenograft model, and increased renal vascularity would result in a mouse null for PEDF. Methods: Tumors were induced in athymic mice using human anaplastic Wilms' tumor cells. Purified PEDF protein or vehicle was administered for 7 days beginning 2 to 3 weeks after inoculation. Tumors were stained with anti-PEDF and anti–Factor VIII antibodies. Mitoses and microvascular density (MVD) were counted per high-power field (hpf). PEDF-null mice were generated on a SV129/C57Bl6 background. Wild-type and null kidneys were assessed for MVD. Results: Mean tumor weight in the 2-week group was 60% less than controls (P <.05). The MVD and mitotic count in treated tumors were significantly less than controls (P <.05). PEDF stained strongly in normal kidneys but was minimal to absent in Wilms' tumor. PEDF-null kidneys had increased MVD compared with wild-type (P <.05). Conclusions: PEDF is expressed strongly in normal murine kidney, and loss of its angioinhibitory activity may contribute to pathologic angiogenesis in Wilms' tumor. Systemic PEDF suppresses WT growth by targeting both the tumor cells and its associated vasculature. J Pediatr Surg 38:336-342. Copyright 2003, Elsevier Science (USA). All rights reserved.

Hepatectomia parcial em cirurgia pediátrica

OBJETIVO: Embora, atualmente, as indicações de hepatectomias em crianças sejam menos frequentes, em alguns casos elas constituem a melhor opção terapêutica. O objetivo deste trabalho é relatar a experiência de dez anos com grandes ressecções hepáticas em pacientes pediátricos. MÉTODO: Foram analisados os dados de doze pacientes submetidos a lobectomia hepática nos serviços de Cirurgia Pediátrica do Hospital da Clínicas da Faculdade de Medicina da Universidade de São Paulo e do Hospital Santa Lydia, em Ribeirão Preto (SP) de 1985 a 1995. RESULTADOS: Foram realizadas oito lobectomias esquerdas e quatro lobectomias direitas. Dez crianças foram operadas por neoplasia e duas por complicações de traumatismo hepático. A idade das dez crianças portadoras de neoplasia variou de seis dias a dezesseis meses, sendo em média 3,8 meses. O diagnóstico histopatológico foi hemangioendotelioma em cinco (50%), hepatoadenoma em dois (20%), hepatoblastoma em dois (20%) e hepatocarcinoma em um (10%). O peso do tumor correspondeu em média a 7,1% do peso do paciente. A duração média da cirurgia foi de 2 horas e 58 minutos. O seguimento pós-operatório variou até 141 meses, sendo em média 76,5 meses. Sete pacientes receberam transfusão de sangue intra-operatória, correspondente a 23,3% de sua volemia, em média. Um deles apresentou recidiva de tumor, necessitando reoperação. Nenhum dos doze pacientes apresentou complicações pós-operatórias. CONCLUSÃO: A hepatectomia parcial é um procedimento difícil tecnicamente, que, no entanto, pode ser realizado com segurança, mesmo em hospitais que não disponham de recursos tecnológicos sofisticados, desde que o cirurgião esteja bem preparado para enfrentar suas dificuldades.

Antitumor activities of iodoacetate and dimethylsulphoxide against solid Ehrlich carcinoma growth in mice.

Treatment of tumor-bearing mice with LD12.5 values of iodoacetate; IAA (1.84 mg/100 g b.w.) and/or dimethylsulphoxide; DMSO (350 mg/100 g b.w.) significantly increased the cumulative mean survival time and percentage of survivors and reduced the mean tumor weight, compared to tumor-bearing controls, however, a more pronounced effect is recorded in the combined treatment. Also, an increase in the life span (ILS%) and tumor growth inhibition ratio (T/C%) are reported and amounted to 145.78 and 43.80%, 195.54 and 61.30% and 220.77 and 78.40% in IAA, DMSO and combined-treated groups, respectively. Results obtained from biochemical studies reveal that a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls. On the other hand, a single DMSO treatment significantly elevated the activities of blood antioxidant enzymes, i.e. glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and decreased the liver RNA and DNA levels. Combined treatment increased significantly the levels of plasma LDH and erythrocytes G6PDH activities, as well as liver glycogen, and in contrast it decreased the levels of liver total protein, RNA and DNA, compared to normal controls.

Aldosterone-secreting adrenocortical carcinomas are associated with unique operative risks and outcomes

Background. Adrenocortical carcinoma (ACC) that produces aldosterone is an extremely rare, uncharacterized endocrine malignancy. Our aim was to characterize this neoplasm in terms of its clinical behavior and patient outcomes. Methods. A retrospective review was made of all patients who had operative management of aldosterone-secreting ACC from 1957 to 2000 at the Mayo Clinic. Comparisons were made to patients with non-aldosterone-secreting ACC treated during the same period. Results. Of 141 patients with ACC, we identified 15 patients with aldosterone-secreting ACC. Isolated aldosterone hypersecretion was present in 10 patients, and mixed hormonal secretion was detected in 5. Mean tumor size and weight were 10.8 cm and 453 g, respectively. Surgical management included curative resection in 10 patients (67%). Perioperative mortality was 20%. Disease recurred in 7 patients (70%) with a median interval of 17 months. Five-year survival was 52%. Patients with aldosterone-secreting ACC had an increased risk of perioperative mortality (20% vs 5%), yet they had an overall survival of 63 months compared to 19 months for patients with non-aldosterone-secreting ACC. Conclusions. Aldosterone hypersecretion occurs in 11% of all ACCs and is associated with unique operative risk and outcome. Although patients harboring aldosterone-secreting ACC appear to have an increased risk of perioperative death, survivors may have an improved overall survival rate compared with patients with non-aldosterone-secreting ACC. (Surgery 2002;132:1008-12.)

Influence of omega-3 fatty acids on the growth of human colon carcinoma in nude mice

The present study investigated the influence of dietary omega-3 fatty acid supplementation on the growth of human colon carcinoma xenograft in athymic nude mice. Four diets were fed to evaluate the effect of levels and types of fat on colon tumor growth. Animals were maintained on a standard diet modified by addition of fats containing omega-3 and omega-6 fatty acids to represent high and low fat intakes for 53 days. The final mean estimated tumor weight for the high fat corn oil (24%) fed group was 2302 mg, whereas the low fat (8% corn oil) group was 1681 mg. The final mean tumor weight of the high fat menhaden oil fed group was 782 mg representing a 66% decrease in growth compared to the high fat corn oil group and a decrease of 54% compared to the low corn oil fed group. The high fat golden algae oil fed group resulted in a mean final tumor weight of 223 mg representing a 90% inhibition of tumor growth relative to the high fat corn oil fed group and 87% inhibition of growth compared to the low fat corn oil fed group. These findings indicate that dietary omega-3 fatty acids possess significant tumor suppressing properties and that the primary tumor suppressing fatty acid is docosahexaenoic acid. Histopathologic examination of control and treated tumors and expression array analyses (human cytokine and apoptosis arrays) support the tumor growth inhibition data and provide evidence for discussion of possible mechanisms for the observed growth inhibition.