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1.
Mucosal Immunol ; 10(2): 481-492, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27381924

RESUMO

Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. Mast cell function during helminth infection was previously studied using mast cell-deficient Kit-mutant mice that display additional mast cell-unrelated immune deficiencies. Here, we use mice that lack basophils or mucosal and connective tissue mast cells in a Kit-independent manner to re-evaluate the impact of each cell type during helminth infection. Neither mast cells nor basophils participated in the immune response to tissue-migrating Strongyloides ratti third-stage larvae, but both cell types contributed to the early expulsion of parasitic adults from the intestine. The termination of S. ratti infection required the presence of mucosal mast cells: Cpa3Cre mice, which lack mucosal and connective tissue mast cells, remained infected for more than 150 days. Mcpt5Cre R-DTA mice, which lack connective tissue mast cells only, and basophil-deficient Mcpt8Cre mice terminated the infection after 1 month with wild-type kinetics despite their initial increase in intestinal parasite burden. Because Cpa3Cre mice showed intact Th2 polarization and efficiently developed protective immunity after vaccination, we hypothesize that mucosal mast cells are non-redundant terminal effector cells in the intestinal epithelium that execute anti-helminth immunity but do not orchestrate it.


Assuntos
Intestino Delgado/imunologia , Mastócitos/imunologia , Strongyloides ratti/imunologia , Estrongiloidíase/imunologia , Células Th2/imunologia , Animais , Carboxipeptidases A/genética , Quimases/genética , Imunidade nas Mucosas , Intestino Delgado/parasitologia , Larva , Mastócitos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Carga Parasitária , Ratos , Ratos Wistar , Triptases/genética
2.
Zentralbl Gynakol ; 127(1): 31-6, 2005 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-15702448

RESUMO

OBJECTIVE: To evaluate mono-institutional results concerning tumor free survival, overall survival, local tumor control and rate of distant metastasis following breast-conserving therapy. PATIENTS AND METHODS: Retrospectively, 274 breast cancer patients who were treated between 1990-1997 in our institution were analysed. The whole breast was homogeneously irradiated (2.0 Gy to 50 Gy), followed by a boost of 10-16 Gy to the tumor bed. Mean follow-up was 55 months. Overall survival, local tumor control and rate of distant metastasis were analysed. RESULTS: Cause-specific survival at 5 years after treatment was 93 %. Within 3 to 60 months following treatment, 18 (7 %) patients suffered from ipsilateral breast recurrence. 24 (9 %) patients developed contralateral carcinoma. Survival from local recurrence (single manifestation) was 78 % at 5 years after treatment, 20 % at 7 years. Occurrence of local failures was significantly correlated to receptor status, contralateral carcinoma, distant metastasis and surgical technique and not to tumor size, margins, grading, nodal status, age or lymphangiosis. 9 % of the patients developed distant metastases, predominantly bone metastases (71 %). Survival from distant metastasis was 64 % at 5 years, 10 % at 7 years. Occurrence of distant metastasis was significantly correlated to grading, tumor size, receptor status, lymphangiosis or local recurrence. CONCLUSION: Our institutional results show that tumor free survival, overall survival, local tumor control and distant failure rate achieved by breast conserving therapy are within the range of literature data.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo
3.
Eur J Cancer ; 38(4): 594-601, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11872355

RESUMO

The aim of the study was to optimise the still unsatisfactory therapeutic results in head and neck cancer by studying the results and the side-effects of radiotherapy, chemotherapy and/or local hyperthermia treatment of human tumour xenografts. Mice carrying human-derived head and neck squamous cell carcinoma xenografts with a mean volume of 100 mm(3) received 5x2 Gy, cisplatin or ifosfamide and/or local hyperthermia at 41/41.8 degrees C. Haematocrit and tumour volumes were determined two or three times per week, respectively, until day 25 or day 60. At day 60, the highest number of complete remissions (CRs) (80%) was observed in the triple modality therapy group with radiation, local hyperthermia at 41.8 C and cisplatin at a dosage of 2 mg/kg body weight (b.w.). Therapeutic side-effects were moderate weight loss and a mild anaemia. Thus, with regard to the long-term tumour-free survival, the most effective treatment was the combination of radiotherapy, cisplatin and local hyperthermia at 41.8 C.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/terapia , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Hipertermia Induzida/efeitos adversos , Radioterapia/efeitos adversos , Animais , Terapia Combinada , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Resultado do Tratamento
4.
Urologe A ; 40(5): 376-9, 2001 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-11594211

RESUMO

Radiotherapy of bladder cancer is a locally effective therapeutic approach. It is increasingly becoming part of the multimodal protocols aimed at the preservation of both organ and organ function. In this context, it is an alternative to cystectomy. The addition of chemotherapy to radiotherapy enhances the curative potential of this non-surgical approach and may be useful especially in older, multimorbid patients. If chemotherapy can not be applied, the use of radiotherapy alone is reasonable, although in advanced tumors the results are disappointing. After the transurethral resection of bladder cancer, postoperative radiotherapy should be considered in muscle-invasive cancer as well as when other negative prognostic factors occur. The prerequisites for an effective, minimally toxic, state of the art radiotherapy are a subtle treatment-planning procedure and an accurate delivery of the radiation.


Assuntos
Carcinoma de Células de Transição/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Terapia Neoadjuvante , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
5.
Urologe A ; 40(5): 380-3, 2001 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-11594212

RESUMO

Radical cystectomy is the current standard therapy for muscle invasive or locally advanced transitional cell carcinoma of the bladder. Organ-preserving monotherapeutic alternatives (e.g. transurethral resection, radiotherapy) do not lead to similar cure rates. In selected cases, a trimodal approach using transurethral resection and combined radio- and chemotherapy can be as efficient as cystectomy.


Assuntos
Carcinoma de Células de Transição/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Radioterapia Adjuvante , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia
6.
Urologe A ; 40(4): 308-12, 2001 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-11490865

RESUMO

Penile cancer is rare. Thus, there are no therapeutic recommendations fulfilling the requirements of evidence-based medicine. The empirically based therapeutic approach consists of local excision, laser therapy, or radiotherapy with comparable local control rates. Radiation is delivered by external beam radiotherapy or as brachytherapy. After radiotherapy, 5-year survival rates of 66-92% and organ preservation in 55-84% are reported. Serious long-term sequelae are necrosis (3-23%) and urethral stenosis (6-45%) requiring surgery. In the adjuvant treatment of the locoregional lymph nodes, lymphadenectomy and radiotherapy of both inguinal regions are therapeutic options. Inguinal lymph node metastases may be irradiated pre- or postoperatively to reduce the local recurrence rates. In addition, palliative radiotherapy of the primary tumor, lymph node, or distant metastases is of use for incurable patients. New combined therapies, e.g., radiochemothermotherapy, are currently under clinical evaluation and may offer a curative and organ-preserving therapeutic option to patients with locally advanced tumors.


Assuntos
Neoplasias Penianas/radioterapia , Braquiterapia , Terapia Combinada , Humanos , Excisão de Linfonodo , Irradiação Linfática , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Neoplasias Penianas/cirurgia , Radioterapia Adjuvante , Taxa de Sobrevida
7.
Urologe A ; 40(4): 313-4, 2001 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-11490866

RESUMO

Some authors report successful use of radiochemotherapy in patients with penile cancer. The most promising chemotherapeutic agents in penile cancer are cisplatin, methotrexate, bleomycin, vinblastine, and vincristine. There are different protocols for the use of chemotherapeutic agents such as mono- or polychemotherapy in combination with radiotherapy. Operative treatment is still the primary approach in patients with penile cancer. However, in some patients with relevant co-morbidity who wish to receive organ-sparing therapy, radiochemotherapy may be applied when low-stage tumors (carcinoma in situ or T1) are present. There is no chemotherapeutic agent of choice to be recommended. The results of radiochemotherapy in patients with T2 tumors or higher are not satisfactory because local tumor control often cannot be achieved.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/radioterapia , Radiossensibilizantes/uso terapêutico , Antineoplásicos/efeitos adversos , Terapia Combinada , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Prognóstico , Radiossensibilizantes/efeitos adversos
8.
Med Phys ; 28(6): 959-65, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11439492

RESUMO

If metallic material is exposed to ionizing radiation of sufficient high energy, an increase in dose due to backscatter radiation occurs in front of this material. Our purpose in this study was to quantify these doses at variable distances between scattering materials and the detector at axial beam angles between 0 degree (zero angle in beams eye view) and 90 degrees. Copper, silver and lead sheets embedded in a phantom of perspex were exposed to 10 MV-bremsstrahlung. The detector we developed is based on the fluorescence property of pyromellitic acid (1,2,4,5 benzenetetracarboxylic acid) after exposure to ionizing radiation. Our results show that the additional doses and the corresponding dose distribution in front of the scattering materials depend quantitatively and qualitatively on the beam angle. The backscatter dose increases with varying beam angle from 0 degree to 90 degrees up to a maximum at 55 degrees for copper and silver. At angles of 0 degree and 55 degrees the integral backscatter doses over a tissue-equivalent depth of 2 mm are 11.2% and 21.6% for copper and 24% and 28% for silver, respectively. In contrast, in front of lead there are no obvious differences of the measured backscatter doses at angles between 0 degree and 55 degrees. With a further increase of the beam angle from 55 degrees to 90 degrees the backscatter dose decreases steeply for all three materials. In front of copper a markedly lower penetrating depth of the backscattered electrons was found for an angle of 0 degree compared to 55 degrees. This dependence from the beam angle was less pronounced in front of silver and not detectable in front of lead. In conclusion, the dependence of the backscatter dose from the angle between axial beam and scattering material must be considered, as higher scattering doses have to be considered than previously expected. This may have a clinical impact since the surface of metallic implants is usually curved.


Assuntos
Metais , Fótons/uso terapêutico , Próteses e Implantes , Radioterapia de Alta Energia/estatística & dados numéricos , Fenômenos Biofísicos , Biofísica , Cobre , Humanos , Chumbo , Aceleradores de Partículas , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , Espalhamento de Radiação , Prata
9.
Strahlenther Onkol ; 177(5): 247-51, 2001 May.
Artigo em Alemão | MEDLINE | ID: mdl-11398610

RESUMO

BACKGROUND: With 17.6% of all primary parotid neoformations the benign Warthin's tumor (cystadenolymphoma) is the second common parotid gland tumor. Males > 50 years are affected predominantly. After surgery the recurrence rate is less than 5%. Histomorphologically the tumor is characterized by cystoid ducts lined by epithelial cells as well as lymphoid stroma. The lymphoid component has been described as radioresponsive whereas the epithelial parts are less radiosensitive. Since 1960 only one patient treated by primary radiotherapy has been published. CASE REPORT: A 77-year-old woman suffered from cystadenolymphoma (maximal diameter 7 cm). Because of its extension and the reduced performance status of the patient surgery was no option. Radiotherapy was performed with a total dose of 50 Gy. Clinically, the tumor regressed completely after 30 Gy, which was confirmed by CT at 6 weeks after completion of radiotherapy. After 6 and 12 months the patient stayed free of tumor. EPICRISIS: In our case the cystadenolymphoma was unusually large (7 cm). Radiotherapy with 50 Gy induced complete tumor regression. The good clinical response after 30 Gy suggests that the necessary dose may be lower for less extended cystadenolymphomas. CONCLUSION: We present a case of cystadenolymphoma treated by radiotherapy with 50 Gy resulting in a complete remission. Due to missing published experiences no common recommendation for the total dose can be given. In the following situations radiotherapy should be considered: 1. high surgical risk of damage to the facial nerve, 2. unfavorable cosmetic outcome after surgery, 3. inoperability for internal risks, 4. refusal of operation.


Assuntos
Adenolinfoma/radioterapia , Neoplasias Parotídeas/radioterapia , Adenolinfoma/diagnóstico por imagem , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Neoplasias Parotídeas/diagnóstico por imagem , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X
10.
Int J Oncol ; 18(6): 1145-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11351243

RESUMO

We developed a mouse model in a representative human derived head and neck cancer cell line for preclinical studies to evaluate antitumor response, tumor-free survival and host toxicity of alkylating agents, antimetabolites, platinum analogs and taxanes alone or in combination. Ninety athymic NMRI mice were inoculated with human derived oral squamous cell carcinoma cells growing on the hind paw to an average volume of 180 +/- 80 mm3. Animals were stratified according to tumor volume into 10 groups (n=6-10) and treated with ifosfamide (65 mg/kg b.w.), docetaxel (24 mg/kg b.w.), cisplatin (2 mg/kg b.w.), carboplatin (6 or 10 mg/kg b.w.), methotrexate (1 mg/kg b.w.), and fluorouracil (15 mg/kg b.w.) intravenously in single agent or combination (ifosfamide plus docetaxel or ifosfamide plus carboplatin) treatment schedules or controls. Tumor volume was measured 3 times per week for 60 days. The average tumor volume, the overall survival time and the response rates (CR, PR) of the treated animals were compared with the data obtained from untreated controls and statistically evaluated. Untreated tumors showed rapid and exponential tumor growth. Single agent therapies with ifosfamide, cisplatinum, and docetaxel lead to significant tumor regression and improved overall survival. Low dose carboplatin monotherapy induced significant tumor growth delay, but not significant tumor regression. Most impressive tumor-free survival was achieved by combination treatment with ifosfamide and docetaxel. This preclinical study demonstrates an animal model capable of differentiating various chemotherapy regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Modelos Animais de Doenças , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Animais , Plaquetas/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Ifosfamida/administração & dosagem , Metotrexato/administração & dosagem , Camundongos , Camundongos Nus , Paclitaxel/administração & dosagem , Taxa de Sobrevida
11.
Int J Radiat Oncol Biol Phys ; 49(5): 1317-25, 2001 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11286840

RESUMO

PURPOSE: To investigate the feasibility and effectiveness of radiochemothermotherapy (triple-modality therapy) in patients with inoperable recurrent breast cancer. PATIENTS AND METHODS: Patients with inoperable recurrent lesions, World Health Organization (WHO) performance status of 2 or greater, life expectancy of more than 3 months, adequate bone marrow, hepatic and renal function were eligible for this Phase I/II study. Conventionally fractionated or hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia (HT) combined with chemotherapy (CT; epirubicin 20 mg/m(2), ifosfamide 1.5 g/m(2)) was applied within 30 min after RT. RESULTS: Twenty-five patients, all heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy. The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The overall response rate was 80% with a complete response (CR) rate of 44%. Response rates in patients with noninflammatory disease (n = 14; CR 10 patients, partial response [PR] 3 patients) were far better than in patients with inflammatory disease (n = 11; CR 1 patient, PR 6 patients). CONCLUSIONS: In patients with recurrent breast cancer, triple-modality therapy is feasible with acceptable toxicity. High remission rates can be achieved in noninflammatory disease, however, local control is limited to a few months. Whether the addition of chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an open question.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Terapia Combinada , Epirubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Ifosfamida/administração & dosagem , Pessoa de Meia-Idade , Dosagem Radioterapêutica
12.
Int J Radiat Oncol Biol Phys ; 49(4): 1119-25, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11240254

RESUMO

PURPOSE: To investigate the influence of different treatment modalities (radiotherapy, chemotherapy, and hyperthermia) on the oxygenation of human tumor xenografts and to correlate it with the tumoricidal effect we conducted this study. METHODS AND MATERIALS: Human-derived head-and-neck squamous cell carcinoma xenografts (implanted in nude mice/nine groups of 10 mice) were treated with various treatment modalities and combinations of them (radiation with 5 x 2 or 10 x 2 Gy, hyperthermia at 41 degrees C or 41.8 degrees C, chemotherapy with ifosfamide [32 mg/kg] or cisplatin [2 mg/kg]). The tumor volume was evaluated 3 times per week until Day 60. Tumor pO(2) was measured at Day 1, 5, 8, and 12 with a polarographic pO(2) histograph. RESULTS: Within treatment time (maximum, 10 days) the median pO(2) increased in all groups (except the control group), concomitantly the fraction of measurements of pO(2) that were less than 10 mm Hg showed a constant decrease (p < or = 0.001). The highest difference between the median pO(2) values and the fraction of measurements of pO(2) that were less than 10 mm Hg at the start and 1 week after the end of therapy occurred in the groups with radiochemothermotherapy (triple-modality therapy; p< or = 0.001). At Day 60, the highest rate of complete remissions was observed in the triple-modality therapy groups. CONCLUSION: Tumor oxygenation under a single or combined cancer treatment is correlated with treatment efficacy in terms of complete remissions at Day 60. The posttherapeutic fraction of measurements of pO(2) that were less than 10 mm Hg correlates even better with the long term tumor free survival than the median pO(2) values or the pretherapeutic fraction of measurements of pO(2) that were less than 10 mm Hg.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Oxigênio/metabolismo , Animais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Hipertermia Induzida , Ifosfamida/uso terapêutico , Camundongos , Camundongos Nus , Prognóstico , Fatores de Tempo , Transplante Heterólogo
13.
Oncol Rep ; 8(2): 219-23, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11182030

RESUMO

Patients with brain metastases in disseminated non-seminomatous germ cell cancer of the testis are treated by combined modality, e.g., cisplatin-containing chemotherapy, whole brain irradiation and/or surgical excision. However, cure rates of patients refractory to that standard treatment are low (5-year survival rate <30%). Preclinical data on the use of hyperthermia combined with selected cytotoxic drugs clearly show increased tumor cell killing compared to chemotherapy alone with no increase in toxicity to normal tissue. These results are consistent with the concept that whole body hyperthermia (WBH) at 41.8 degrees C is non-myelosuppressive and can potentiate the tumoricidal effects of specific chemotherapeutic agents, thus improving the therapeutic index. We report on a patient with embryonal testicular cancer presenting with lung, liver and brain metastases who initially underwent orchiectomy, whole brain irradiation and cisplatin-containing chemotherapy. Restaging revealed minor regression of brain and lung metastases and no change of liver metastases. However, beta-HCG values dropped from initial 400000 mIU/ml to 12 mIU/ml with a normal alpha-fetoprotein all the time. Then, two cycles of whole body hyperthermia (WBH) plus chemotherapy were performed, followed by one cycle of chemotherapy without WBH. Radiotherapy, WBH and chemotherapy were well tolerated, especially no neurologic sequelae occurred. After more than 5 years of follow-up, the patient is still alive and disease-free. WBH plus chemotherapy seems to be feasible and may contribute to long-term survival in patients with advanced stages of non-seminomatous germ cell cancer refractory to standard treatment.


Assuntos
Neoplasias Encefálicas/secundário , Germinoma/terapia , Hipertermia Induzida , Neoplasias Testiculares/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/terapia , Terapia Combinada , Germinoma/patologia , Germinoma/radioterapia , Germinoma/secundário , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Estadiamento de Neoplasias , Neoplasias Testiculares/patologia , Neoplasias Testiculares/radioterapia , Fatores de Tempo , Resultado do Tratamento
14.
Mund Kiefer Gesichtschir ; 4 Suppl 2: S423-7, 2000 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-11094509

RESUMO

The potential of distraction osteogenesis in mandibular reconstruction has been limited by its questionable efficacy in previously irradiated bone. The possible osteogenetic effect of recombinant human basic fibroblast growth factor (bFGF) on lengthening of irradiated mandibles was investigated in beagle dogs. We studied nine adult dogs which underwent a full course of external beam radiation therapy (60 Gy/30 fractions). Six months after completion of radiotherapy, the molars were extracted bilaterally followed by bone lengthening of the mandible using an intraoral device. On postoperative day 3 and 7 we injected 10 micrograms bFGF into the osteotomy site of each right hemimandible. The left sides were used as controls. The time course in ossification of the distracted area was evaluated at 2, 4, and 6 weeks after completion of bone lengthening. The radiographs of the newly formed bone tissue were measured by digital image analysis. Corresponding to the radiographic findings, the histological examination of the removed jaws showed an earlier and more intensive bone formation in the treated side after 2, 4, and 6 weeks compared to the control side. We conclude that bFGF promotes the ossification of distracted mandibles after radiation therapy in dogs.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Mandíbula/efeitos dos fármacos , Osteogênese por Distração , Adulto , Animais , Regeneração Óssea/efeitos da radiação , Cães , Humanos , Masculino , Mandíbula/patologia , Mandíbula/efeitos da radiação , Osteorradionecrose/patologia , Proteínas Recombinantes/farmacologia
15.
Strahlenther Onkol ; 175 Suppl 4: 18-22, 1999 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-10584135

RESUMO

PURPOSE: Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine. We investigated this issue in a randomized trial comparing radiochemotherapy (RCT) versus radiochemotherapy and amifostine (RCT + A) in patients with head and neck cancer. PATIENTS AND METHODS: Forty-seven patients with pharyngeal or laryngeal cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RCT alone (21 patients) or RCT + A (21 patients). Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2). Chemotherapy consisted of 70 mg/m2 carboplatin and was administered over 5 days in the 1st and 5th week of the radiotherapy course. 250 mg amifostine were applied daily just before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for xerostomia no patients with laryngeal cancer were assessed because in these cases only small volumes of the salivary glands were within the treatment volume. To evaluate the overall toxicity a summarized CTC score of all observed side effects was calculated. RESULTS: Forty-two patients were evaluable. Clinical characteristics (age, sex, Karnofsky index, tumor-staging) were well balanced in both treatment groups (Tables 2 and 3). Amifostine provided reduction in xerostomia and mucositis (Figures 5 and 6) but had no obvious influence on Karnofsky index, body weight, cutaneous side effects and alopecia (Figures 1 to 4). CONCLUSIONS: According to our preliminary results amifostine has a radioprotective effect on salivary glands. Mucositis can be reduced during radiochemotherapy. At this point of patient accrual the difference between both groups are statistically not significant. To improve the radioprotective effects of amifostine in clinical practice the application of a higher dose (> 250 mg) seems to be necessary.


Assuntos
Amifostina/farmacologia , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Protetores contra Radiação/farmacologia , Radioterapia/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Amifostina/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Prospectivos , Protetores contra Radiação/administração & dosagem , Dosagem Radioterapêutica , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/efeitos da radiação , Estomatite/etiologia , Estomatite/prevenção & controle , Fatores de Tempo , Xerostomia/etiologia , Xerostomia/prevenção & controle
16.
Int J Hyperthermia ; 15(3): 237-50, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10365691

RESUMO

The vascularization of tumours is a critical parameter of their growing and metastatic behaviour. However, little is known about the morphologic reactions of the microvasculature, especially the capillary bed of tumours and the adjacent tissue. In this study, the vessels in MX1 xenotransplants in athymic nu/nu nude mice were quantified and the angioarchitecture was visualized with the aim of presenting stereologic parameters of vessels based on a morphometric analysis of post mortem tissue blocks which were processed by standard histological procedures. In order to study changes of the microvasculature of MX1 tumours, the xenotransplanted nude mice were treated by different therapeutic regimens. Standardized hyperthermia, ifosfamide and irradiation therapies were applied. Special interest was focused on early changes of capillaries and of the pre- as well as post-terminal vascular bed. The stereologic evaluation of capillaries and larger vessels immediately after the therapy with ifosfamide and hyperthermia shows an increase of the mean capillary sizes. Furthermore, tumour samples after the 5th day of irradiation (5 x 2 Gy) and combinations of irradiation and chemotherapy treatment have been investigated. After 5 days of irradiation, a significant decrease of the vascular density was found. The results presented here clearly show that the timing and the mode of therapy influence the capillary morphology and periterminal vasculature of xenotransplanted MX1 tumours.


Assuntos
Neoplasias Experimentais/irrigação sanguínea , Neoplasias Experimentais/terapia , Animais , Antineoplásicos Alquilantes/uso terapêutico , Capilares/patologia , Terapia Combinada , Feminino , Humanos , Hipertermia Induzida , Ifosfamida/uso terapêutico , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Experimentais/radioterapia , Transplante Heterólogo
17.
Strahlenther Onkol ; 174 Suppl 3: 40-3, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9830455

RESUMO

BACKGROUND: Radiotherapy in cancer of the head and neck induces cutaneous and mucosal reactions. These must be carefully assessed and documentated to control the accuracy of individual treatment, the overall toxicity of particular treatment schedules, the efficacy of prophylaxis and treatment and to determine the adequate therapy of treatment sequelae depending on the severity of the reactions. The accurate classification of lesions according to internationally accepted schedules (WHO/RTOG/CTC) is indispensable for the comparison of radiotherapy treatment results and efficacy of supportive care. METHODS: While the treatment of cancer depends on tumor stage and medical circumstances of the patient and is more or less standardized, prophylaxis and treatment of side-effects is highly variable. Discussing an optimized prophylaxis and therapy of oral mucositis, the problem of accurate classification and documentation emerged. The verbal description of mucosal lesions is open to many subjective interpretations. Photographic documentation seems a suitable method to optimize the grading of toxicity. RESULTS: A photographic survey of typical lesions for each grade of toxicity is a tool to reach several aims in one step. Toxicity of an individual patient may be compared with representative photographic examples in daily routine to decide quickly on the grade of toxicity. Subjective differences due to intra- and interpersonal variability of the evaluating radiooncologist will be reduced. The efficacy of treatment can be proven by accurate documentation. Randomized clinical studies concerning prophylaxis and treatment of oral mucositis will provide more reliable results if evaluation of toxicity grading is standardized by photographs. CONCLUSIONS: Photographic documentation of lesions of the oral mucosa might be the best means to reduce interindividual subjectivity in grading. It is a valuable appendix to standard classification systems and only concerns the visible signs of mucosal lesions. However, the exact grading of mucositis is only possible with additional clinical information about pain and nutritional situation.


Assuntos
Documentação/métodos , Mucosa Bucal/efeitos da radiação , Neoplasias/radioterapia , Lesões por Radiação/classificação , Radioterapia/efeitos adversos , Documentação/normas , Alemanha , Humanos , Mucosa Bucal/patologia , Estadiamento de Neoplasias , Neoplasias/patologia , Fotografação , Controle de Qualidade , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radioterapia/normas , Sociedades Médicas
18.
Strahlenther Onkol ; 174(9): 478-81, 1998 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-9765690

RESUMO

PURPOSE: Extracranial metastases of malignant gliomas are rare. We report 2 cases with spinal metastases in patients suffering from glioma. PATIENTS AND METHOD: Two patients (33 and 57 years old) developed spinal canal metastases of a glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and 9 months after surgical resection and radiotherapy. Both metastases were confirmed pathohistologically. RESULTS: Intraspinal metastases were irradiated with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one patient due to reduced clinical condition. Regression of neurological symptoms was observed in the second patient. CONCLUSIONS: Spinal spread of malignant glioma should be considered during care and follow-up in glioma patients with spinal symptoms.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Adulto , Feminino , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Neoplasias da Coluna Vertebral/diagnóstico por imagem
19.
Strahlenther Onkol ; 174(7): 355-7, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9689956

RESUMO

BACKGROUND: At the University of Lübeck, radiotherapy is delivered by a 6/18-MV linear accelerator. Using the integrated multileaf collimator, irradiation of individually shaped treatment fields is possible in place of alloy blocks. Due to unsatisfactory pretherapeutic review of the radiation-field-specific multileaf collimator (MLC) configuration, we developed a simulation-multileaf collimator (SMLC) and assessed its feasibility at different tumor sites. MATERIAL AND METHODS: The SMLC is made of a perspex carrier with 52 horizontal sliding leaves. The position of each leaf is calculated by a 3D treatment-planning computer. The technician manually adjusts the leaves according to the beams-eye-view plot of the planning computer. Consequently, the SMLC is mounted on the therapy simulator at a distance of 64.8 cm from the focus. The treatment fields and the position of the leaves are documented by X-ray films. RESULTS: Using the SMLC, radiation oncologists are able to review exactly the leaf configuration of each MLC-shaped radiation field and to correlate the MLC-shaped radiation field with the treated volume, the organs at risk and the port films acquired by the Portal Vision system. CONCLUSION: The SMLC is a new tool to review radiation planning that uses an MLC in daily routine. The use of the SMLC improves the documentation and the quality assurance. It accelerates the treatment field review at the linear accelerator by comparing the SMLC simulator films with the portal images.


Assuntos
Simulação por Computador , Processamento de Imagem Assistida por Computador/instrumentação , Neoplasias/radioterapia , Aceleradores de Partículas , Planejamento da Radioterapia Assistida por Computador/instrumentação , Tomografia Computadorizada por Raios X/instrumentação , Calibragem , Feminino , Humanos , Masculino , Imagens de Fantasmas
20.
Anticancer Res ; 17(4B): 2895-7, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9329557

RESUMO

The combination of ionizing irradiation and local hyperthermia therapy has been demonstrated to be efficacious in a variety of localized neoplasms. One of the most consistent conclusions from this experience, however, is the finding that large tumor size is a significant negative prognosticator for attaining complete tumor regression. During the past decade investigators have begun to look at the possibility of adding chemotherapy to thermo-radiotherapy in order to improve the efficacy of treatment in patients with large tumors. This review article summarizes the recent clinical experience with such triple modality therapy.


Assuntos
Hipertermia Induzida , Neoplasias/terapia , Antineoplásicos/uso terapêutico , Terapia Combinada , Humanos
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