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5-Hydroxy-3',4',6,7-tetramethoxyflavone (TMF) is a plant-origin flavone known for its anti-cancer properties. In the present study, the cytotoxic effect of TMF was evaluated in the U87MG and T98G glioblastoma (GBM) cell lines. The effect of TMF on cell viability was assessed with trypan blue exclusion assay and crystal violet staining. In addition, flow cytometry was performed to examine its effect on the different phases of the cell cycle, and in vitro scratch wound assay assessed the migratory capacity of the treated cells. Furthermore, the effect of in vitro radiotherapy was also evaluated with a combination of TMF and radiation. In both cell lines, TMF treatment resulted in G0/G1 cell cycle arrest, reduced cell viability, and reduced cell migratory capacity. In contrast, there was an antagonistic property of TMF treatment with radiotherapy. These results demonstrated the antineoplastic effect of TMF in GBM cells in vitro, but the antagonistic effect with radiotherapy indicated that TMF should be further evaluated for its possible antitumor role post-radiotherapy.
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Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Glioblastoma/metabolismo , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proliferación Celular , Apoptosis , Supervivencia CelularRESUMEN
Glioblastoma is one of the most malignant and lethal forms of primary brain tumors in adults. Linearol, a kaurane diterpene isolated from different medicinal plants, including those of the genus Sideritis, has been found to possess significant anti-oxidant, anti-inflammatory and anti-microbial properties. In this study, we aimed to determine whether linearol could exhibit anti-glioma effects when given alone or in combination with radiotherapy in two human glioma cell lines, U87 and T98. Cell viability was examined with the Trypan Blue Exclusion assay, cell cycle distribution was tested with flow cytometry, and the synergistic effects of the combination treatment were analyzed with CompuSyn software. Linearol significantly suppressed cell proliferation and blocked cell cycle at the S phase. Furthermore, pretreatment of T98 cells with increasing linearol concentrations before exposure to 2 Gy irradiation decreased cell viability to a higher extent than linearol or radiation treatment alone, whereas in the U87 cells, an antagonistic relationship was observed between radiation and linearol. Moreover, linearol inhibited cell migration in both tested cell lines. Our results demonstrate for the first time that linearol is a promising anti-glioma agent and further studies are needed to fully understand the underlying mechanism of this effect.
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Neoplasias Encefálicas , Diterpenos , Glioblastoma , Glioma , Humanos , Glioblastoma/metabolismo , Glioma/patología , Diterpenos/uso terapéutico , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Neoplasias Encefálicas/metabolismoRESUMEN
Radiation therapy plays an important role in almost every cancer treatment. However, radiation toxicity to normal tissues, mainly due to the generation of reactive free radicals, has limited the efficacy of radiotherapy in clinical practice. Curcumin has been reported to possess significant antitumor properties. Although curcumin can sensitize cancer cells to irradiation, healthy cells are much less sensitive to this effect, and thus, curcumin is thought to be a potent, yet safe anti-cancer agent. In this review, a summary of the role of curcumin as both a radiosensitizer and radioprotector has been presented, based on the most recent data from the experimental and clinical evaluation of curcumin in different cancer cell lines, animal models, and human patients.
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Curcumin, a bioactive polyphenol, is known to have anticancer properties. In this study, the effectiveness of curcumin pretreatment as a strategy for radio-sensitizing glioblastoma cell lines was explored. For this, U87 and T98 cells were treated with curcumin, exposed to 2 Gy or 4 Gy of irradiation, and the combined effect was compared to the antiproliferative effect of each agent when given individually. Cell viability and proliferation were evaluated with the trypan blue exclusion assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic effects of the combination treatment were analyzed with CompuSyn software. To examine how the co-treatment affected different phases of cell-cycle progression, a cell-cycle analysis via flow cytometry was performed. Treatment with curcumin and radiation significantly reduced cell viability in both U87 and T98 cell lines. The combination treatment arrested both cell lines at the G2/M phase to a higher extent than radiation or curcumin treatment alone. The synergistic effect of curcumin when combined with temozolomide resulted in increased tumor cell death. Our results demonstrate for the first time that low doses of curcumin and irradiation exhibit a strong synergistic anti-proliferative effect on glioblastoma cells in vitro. Therefore, this combination may represent an innovative and promising strategy for the treatment of glioblastoma, and further studies are needed to fully understand the molecular mechanism underlying this effect.
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Although several antipsychotic drugs have been shown to possess anticancer activities, haloperidol, a "first-generation" antipsychotic drug, has not been extensively evaluated for potential antineoplastic properties. The aim of this study was to investigate the antitumoral effects of haloperidol in glioblastoma (GBM) U87, U251 and T98 cell lines, and the effects of combined treatment with temozolomide (TMZ) and/or radiotherapy, using 4 Gy of irradiation. The viability and proliferation of the cells were evaluated with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, using the annexin-propidium iodide (PI), and cell cycle, cluster of differentiation (CD) expression and caspase-8 activation were measured using flow cytometry. Treatment with haloperidol significantly reduced cell viability in U87, U251 and T98 GBM cell lines. Haloperidol induced apoptosis in a dose-dependent manner, inhibited cell migration and produced an alteration in the expression of CD24/CD44. The additional effect of haloperidol, combined with temozolomide and radiation therapy, increased tumor cell death. Haloperidol was observed to induce apoptosis and to increase caspase-8 activation. In conclusion, haloperidol may represent an innovative strategy for the treatment of GBM and further studies are warranted in glioma xenograft models and other malignancies.
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INTRODUCTION: Heterotopic ossification may develop after major hip surgeries, thus preventive strategies including radiation therapy and non steroid anti-inflammatory drugs are commonly employed. There are certain concerns regarding the effects of radiation therapy on implant loosening and carcinogenesis. Our study aims to evaluate whether radiation therapy results in implant loosening or radiation-induced tumours in the long term. PATIENTS AND METHODS: This was a prospective study including 97 high-risk patients for heterotopic ossification who underwent total hip arthroplasty. Patients were divided into 2 groups and received either a combination of radiation therapy and indomethacin (Group A), or indomethacin alone (Group B). Evaluated outcomes included implant loosening or development of radiation-induced tumours during the follow-up period. RESULTS: The follow-up period of the study was 10 years. Group A consisted of 50 patients, while Group B consisted of 47 patients. 3 patients died during the follow-up. There were 2 cases of implant loosening, 1 from each of the 2 groups at 9 and 10 years after surgery respectively; thus, no statistically significant difference regarding implant loosening was found (p < 0.05). During the follow-up period no cases of radiation-induced tumours were identified. CONCLUSION: Our results are consistent with those of other studies supporting the safety of radiation therapy as a preventive strategy for heterotopic ossification following major surgeries in high risk patients. Further studies with even longer follow-up may be required to definitely exclude the possibility of adverse outcomes linked with radiation therapy.
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Antiinflamatorios no Esteroideos/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Indometacina/uso terapéutico , Osificación Heterotópica/prevención & control , Osificación Heterotópica/radioterapia , Complicaciones Posoperatorias/prevención & control , Anciano , Anciano de 80 o más Años , Carcinogénesis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osificación Heterotópica/etiología , Osteoartritis de la Cadera/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/radioterapia , Estudios Prospectivos , Falla de PrótesisRESUMEN
BACKGROUND/AIM: The aim of the study was to investigate whether E-cadherin and syndecan-1 are molecular markers of advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The expression of E-cadherin and syndecan-1 (SDC1) was examined immunohistochemically on tissue specimens of 64 patients, with stage III disease at presentation. The obtained expression data were correlated with clinical parameters. RESULTS: Negative expression of SDC1 was correlated with squamous histology (p=0.002). E-cadherin positive expression was significantly associated with increased 2-year overall survival (OS) rate (p=0.032). In the multivariate Cox analysis, performance status 0-1 was an independent predictor of OS (p=0.001) and disease-free survival (DFS) (p=0.001). E-cadherin expression was an independent predictor of OS (p=0.007) and DFS (p=0.029). CONCLUSION: E-cadherin might be a prognostic factor for OS and DFS in advanced stage NSCLC patients. Further investigations are needed for the establishment of E-cadherin and syndecan-1 as molecular markers, affecting treatment response and survival.
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Antígenos CD/metabolismo , Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioradioterapia/mortalidad , Neoplasias Pulmonares/patología , Sindecano-1/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Adenocarcinoma/terapia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancer. Another promising cancer therapy is difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, which is oraly administered and well tolerated. Nevertheless, many types of cancer, including gliomas, have exhibited resistance to TRAIL-induced apoptosis and similarly the potency of DFMO should be enhanced to optimize therapeutic efficacy. In this study we sought to determine whether DFMO, in combination with TRAIL and radiation, could result in an enhanced anti-glioma effect in vitro. We investigated the effect of DFMO, TRAIL and radiation in various combinations on a panel of glioblastoma cell lines (A172, T98G, D54, U251MG). Viability and proliferation of the cells were examined with trypan blue exclusion assay, crystal violet and xCELLigence system. Apoptosis (Annexin-PI), cell cycle and activation of caspase-8 were tested with flow cytometry. BAD protein levels were determined by Western blot analysis. DFMO induced BAD overexpression. Combination treatment with DFMO, TRAIL and radiation significantly reduced cell viability in all cell lines tested. Increased induction of cell death and cell cycle arrest was confirmed with flow cytometry in A172 and D54 cell lines, while enhanced activation of annexin and caspase-8 was revealed in U251MG and T98G cells. The treatment of glioblastoma cell lines with combination of DFMO, TRAIL and radiation showed an enhanced effect. This combination treatment may represent a novel strategy for targeting glioblastoma.
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Neoplasias Encefálicas/terapia , Eflornitina/farmacología , Glioma/terapia , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Western Blotting , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Adhesión Celular/efectos de los fármacos , Adhesión Celular/efectos de la radiación , Movimiento Celular/efectos de los fármacos , Movimiento Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Terapia Combinada , Citometría de Flujo , Glioma/metabolismo , Glioma/patología , Humanos , Dosis de Radiación , Células Tumorales Cultivadas , Rayos XRESUMEN
BACKGROUND: Preoperative chemoradiation (CRT) is considered the standard of care in the management of stage II/III rectal cancer. The aim of this retrospective study was to assess the efficacy and safety of preoperative CRT in our patient cohort with locally advanced rectal adenocarcinoma. METHODS: Forty patients with cT3-4N0-2M0 adenocarcinoma of the lower (n = 26) and mid/upper (n = 14) rectum were enrolled in this study between 2001 and 2012. Radiotherapy (RT) was given to the pelvis. The median prescribed dose was 45 Gy (daily dose, 1.8 - 2.0 Gy). All patients received chemotherapy concurrently with RT and underwent surgery 6 - 8 weeks after CRT. Low anterior resection (LAR) was achieved in 21 patients. Total mesorectal excision (TME) was performed in 24 patients. RESULTS: Tumor downstaging (expressed as TN downstaging) was observed in 15 patients (38%); a pathological complete response (pCR) was pathologically confirmed in six of them. In nine out of the 26 (23%) patients with low lying tumors, sphincter preservation (SP) was possible. SP was also possible in all but one patient (13%) who achieved a pCR. In three out of 15 patients (8%) with preoperative sphincter infiltration, SP was achieved. With a median follow-up of 58 months, the 4-year local control (LC), distant metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) rates were 89.7%, 86.9%, 79.5% and 81.2%, respectively. The pretreatment tumor size was predictive of response to preoperative CRT. The response to preoperative CRT did show a significant impact on DFS and on OS. TME resulted in a statistically significant increased DFS rate. No grade 3/4 acute toxicity was reported. Three patients developed grade 3 late side effects. CONCLUSION: Preoperative CRT demonstrates encouraging rates of disease control and facilitates complete resection and SP in advanced rectal cancer with acceptable late toxicity.
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INTRODUCTION: Treatment induced necrosis is a relatively frequent finding in patients treated for high-grade glioma. Differentiation by imaging modalities between glioma recurrence and treatment induced necrosis is not always straightforward. This is a comparative study of diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI and (99m)Tc-Tetrofosmin brain single-photon emission computed tomography (SPECT) for differentiation of recurrent glioma from treatment induced necrosis. METHODS: A prospective study was made of 30 patients treated for high-grade glioma who had suspected recurrent tumor on follow-up MRI. All had been treated by surgical resection of the tumor followed by standard postoperative radiotherapy with chemotherapy. No residual tumor had been found on brain imaging immediately after the initial treatment. All the patients were studied with dynamic susceptibility contrast brain MRI and, within a week, (99m)Tc-Tetrofosmin brain SPECT. RESULTS: Both (99m)Tc-Tetrofosmin brain SPECT and dynamic susceptibility contrast MRI could discriminate between tumor recurrence and treatment induced necrosis with 100% sensitivity and 100% specificity. An apparent diffusion coefficient (ADC) ratio cut-off value of 1.27 could differentiate recurrence from treatment induced necrosis with 65% sensitivity and 100% specificity and a fractional anisotropy (FA) ratio cut-off value of 0.47 could differentiate recurrence from treatment induced necrosis with 57% sensitivity and 100% specificity. A significant correlation was demonstrated between (99m)Tc-Tetrofosmin uptake ratio and rCBV (P=0.003). CONCLUSIONS: Dynamic susceptibility contrast MRI and brain SPECT with (99m)Tc-Tetrofosmin had the same accuracy and may be used to detect recurrent tumor following treatment for glioma. DTI also showed promise for the detection of recurrent tumor, but was inferior to both dynamic susceptibility contrast MRI and brain SPECT.
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Neoplasias Encefálicas/diagnóstico , Encéfalo/patología , Quimioradioterapia/efectos adversos , Imagen de Difusión Tensora/métodos , Glioma/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Traumatismos por Radiación/patología , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/terapia , Medios de Contraste , Diagnóstico Diferencial , Femenino , Glioma/terapia , Humanos , Masculino , Persona de Mediana Edad , Necrosis/etiología , Necrosis/patología , Recurrencia Local de Neoplasia/prevención & control , Compuestos Organofosforados , Compuestos de Organotecnecio , Traumatismos por Radiación/etiología , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis. METHODS: Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A) (subcutaneously, 500 mg flat dose) before radiotherapy or radiotherapy alone (R). Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria. RESULTS: A total 44 patients were enrolled in this trial, the majority with rectal (20 patients) and cervical cancer (12 patients) and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9%) were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4). Of them, 6 patients belonged to the A group (6/21, 28.6%) and 12 to the R group (12/23, 52.2%). Acute and grade IV radiation colitis was only developed in four patients (17.4%) in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury. CONCLUSIONS: Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.
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Amifostina/uso terapéutico , Colitis/tratamiento farmacológico , Neoplasias Pélvicas/radioterapia , Traumatismos por Radiación/tratamiento farmacológico , Protectores contra Radiación/uso terapéutico , Adulto , Anciano , Colitis/diagnóstico , Colitis/etiología , Terapia Combinada , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pélvicas/complicaciones , Pronóstico , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/diagnóstico , Neoplasias del Recto/complicaciones , Neoplasias del Recto/radioterapia , Tasa de Supervivencia , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
We report an unusual case of solitary osteolytic tibial metastasis from a primary endometrial cancer in a 62-year-old woman. The primary cancer was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy combined with postoperative external beam radiotherapy, while the tibial metastasis was treated with an above knee amputation. The rarity of the case lies on the fact that metastases distally to the elbow and knee are uncommon and endometrial cancer rarely gives distal bone metastases and particularly solitary to the extremities.
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INTRODUCTION: The expression of E-cadherin, beta-catenin and topoisomerase II has been associated with clinical outcome of several cancers including sarcomas. We aimed to evaluate the expression of these markers in leiomyosarcomas (LMS). MATERIALS AND METHODS: Paraffin blocks of 19 primary, nonmetastatic LMS were analysed immunohistochemically for the expression of the above-mentioned markers with a cutoff level for positivity of 20% of cell staining. RESULTS: Expression of E-cadherin was negative in all LMS. Nuclear expression of beta-catenin was also negative in all cases, while positive cytoplasmic beta-catenin expression was observed in approximately half of the patients. The majority of LMS had expression of topoisomerase IIalpha, although only in 10 patients was this expression in more than 20% of tumour cells. From the analysed factors, tumour size was statistically significantly correlated with relapse-free survival. CONCLUSIONS: Further evidence with larger series is required in order to determine the implication of these markers in LMS.
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Antígenos de Neoplasias/metabolismo , Cadherinas/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN/metabolismo , Leiomiosarcoma/metabolismo , beta Catenina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Leiomiosarcoma/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: :Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty. The aim of this study was to evaluate the efficacy of combined radiotherapy and indomethacin as compared to indomethacin alone for the prevention of HO after hip arthroplasty. PATIENTS AND METHODS: 96 patients were prospectively enrolled to receive either a single dose of postoperative radiotherapy of 7.0 Gy and indomethacin for the first 15 postoperative days or indomethacin alone for the same period. A historical group of 50 patients that received indomethacin alone served as control. Primary endpoint was the radiographic evidence of HO at 6 months. Secondary endpoints were the evaluation of factors related to HO development, side effects from each treatment, and group differences in the clinical assessment with the Merle d'Aubigné Score. RESULTS: Four patients in the combined-therapy group developed HO compared to 13 patients in the indomethacin group (p < 0.05) and 13 patients in the historical group (p < 0.05). One patient each in the combined group and the historical group developed Brooker III HO (nonsignificant difference). Duration of surgery and congenital hip disease were associated with HO development in the indomethacin groups, while age and congenital hip disease showed such an association in the combined-therapy group. The side effects and mean Merle d'Aubigné Score did not differ significantly between the three groups. CONCLUSION: Combined radiotherapy and indomethacin was more efficacious in preventing HO after total hip arthroplasty compared to indomethacin alone and should be considered for future investigation.
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Antiinflamatorios no Esteroideos/uso terapéutico , Artroplastia de Reemplazo de Cadera , Indometacina/uso terapéutico , Osificación Heterotópica/prevención & control , Osificación Heterotópica/radioterapia , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osificación Heterotópica/etiología , Dosificación Radioterapéutica , Factores de Riesgo , Resultado del TratamientoRESUMEN
Metastases to the tonsillar fossa due to hematogenous dissemination is an extremely rare phenomenon associated with advanced-stage disease and poor prognosis. In the present report we describe a case of cutaneous melanoma with a metastasis to the tonsil approximately 4 years after the initial diagnosis of the primary disease treated with palliative radiation therapy.
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Melanoma/secundario , Neoplasias Cutáneas/patología , Neoplasias Tonsilares/secundario , Anciano , Humanos , Masculino , Melanoma/radioterapia , Cuidados Paliativos/métodos , Neoplasias Tonsilares/radioterapiaRESUMEN
This study is a presentation of our department's experience in the treatment of localized prostate cancer with either radical or postoperative radiotherapy (RT). Fifty-five patients with clinical localized prostate cancer were reviewed. Thirty-three patients (T1-T2AN0M0 stage) were treated with radical RT and 22 (T2B-T3N0M0 stage) with postoperative RT. All patients received hormonal therapy. Primary end points of the study were the incidence of clinical and biochemical recurrences and death in the whole group and according to treatment modality. Within a median follow-up of 18 months the overall incidence of clinical relapse was 16.9%, of biochemical relapse 12.7% and of death 10.9%. Both treatment options achieved similar outcomes despite the fact that the patients in the postoperative RT group were of higher stage. Radical RT group tended to have better overall and disease-free survival compared to postoperative RT group, but there was no statistically significant evidence. Long-term toxicity was negligible.
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Neoplasias de la Próstata/radioterapia , Anciano , Terapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Radioterapia AdyuvanteRESUMEN
Although the very high locoregional recurrence rates reported with limited D0/D1 surgery can be reduced with extended D2 gastrectomy for operable gastric cancer, overall relapse and survival rates remain poor and can only be improved with adequate perioperative adjuvant treatment. However, despite intensive research, no regimen has been established as standard. Meta-analyses have demonstrated a marginal survival benefit with adjuvant chemotherapy. Two recent large randomized trials for operable gastric cancer, the MAGIC trial and the INT-0116 trial, provide evidence that some patients may benefit from perioperative chemotherapy and chemoradiation, respectively. However, while both trials suggest an overall survival benefit with adjuvant treatment, they don't provide the harm-benefit ratio for specific subsets of patients wih different extent of surgery (D1 or D2) and tumor stage (early [T1,2]/advanced [T3,4]). This lack of evidence complicates current therapeutic adjuvant decisions. Estimating the risk of local and distant recurrence (high, moderate or low) after D1 or D2 surgery in various tumor stages and the expected harm-benefit ratio, the authors provide useful information for decisions on adjuvant chemotherapy with or withour radiotherapy in individual patients. Research on newer cytotoxic and targeted agents may improve treatment efficacy. Simultaneously, advances with microarray-based gene-expression profiling signatures may improve individualized treatment decisions. However, the validation and translation of these genomic classifiers as biomarkers into a completed 'bench-to-bedside' cycle for tailoring treatment to individuals is a major challenge and limits inflated expectations.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gastrectomía/métodos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/radioterapia , Quimioterapia Adyuvante , Terapia Combinada , Toma de Decisiones , Humanos , Terapia Neoadyuvante , Complicaciones Posoperatorias , Pronóstico , Radioterapia Adyuvante , Neoplasias Gástricas/cirugíaRESUMEN
The combination of radiotherapy and indomethacin for the prevention of heterotopic ossification (HO) in high-risk patients undergoing total hip arthroplasty (THA) has not been reported. The aim of the present study was to present the experience of our department with this combined therapeutic protocol. Fifty-four patients who underwent THA received a single dose of 7 Gy of postoperative radiotherapy and 75 mg of indomethacin for 15 days. Patients were analyzed for clinical and radiographical evidence of HO development at 1 year postoperatively. The overall radiographical incidence of HO was 20.4% (95% CI 10.6-33.5%), while only 1 patient with clinically significant HO was seen. Patients with secondary arthritis due to congenital hip disease had a statistically significantly higher incidence of HO compared with those with osteoarthrosis. The clinical assessment with the Merle d'Aubigné score showed that patients with radiographic documentation of HO had a lower mean score compared with those with no evidence of HO. No treatment-related side effects were seen. Combined radiotherapy and indomethacin was effective in preventing heterotopic ossification after total hip arthroplasty. The evaluation of this efficacy compared with radiotherapy or NSAIDs alone should be the future target of larger randomized designs.
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Antiinflamatorios no Esteroideos/uso terapéutico , Artroplastia de Reemplazo de Cadera , Indometacina/uso terapéutico , Osificación Heterotópica/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osificación Heterotópica/diagnóstico por imagen , Osificación Heterotópica/tratamiento farmacológico , Osificación Heterotópica/radioterapia , Radiografía , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
The aim of the present study was to evaluate the association of vascular endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, with tumor grade, microvessel density (MVD) and clinical outcome in patients with soft tissue sarcomas (STSs). Tissue specimens of 28 patients with STSs were analyzed immunohistochemically using specific monoclonal antibodies. Tissue samples were obtained prior to any treatment. Half of the STSs exhibited strong expression of VEGF that was associated statistically significantly with high tumor grade. Strong expression of KDR/Flk-1 was detected in only 2 sarcomas. No association was demonstrated between VEGF and KDR/Flk-1 expression. MVD was significantly associated with tumor grade and was higher in sarcomas with strong VEGF expression. Limited data on clinical outcome precluded solid analyses for an association with disease progression. This study provides further evidence on the role of VEGF and MVD in tumor aggressiveness in STSs.