RESUMEN
Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral part of multidisciplinary treatment of advanced germ cell cancer; however, it is associated with a high complications rate. The present study aimed to describe sexual disorders in 53 patients with testicular cancer who underwent full bilateral, non-nerve-sparing PC-RPLND in our institution, focusing beyond ejaculatory dysfunction. The International Index for Erectile Function (IIEF) questionnaire was used as diagnostic tool of male sexual functioning pre-operatively and three months after RPLND, while post-operatively patients were asked to describe and evaluate changes in selected sexual parameters. Study findings demonstrate mixed pattern of changes in sexual functioning, with no difference in erectile functioning before and after operation. However, orgasmic function and intercourse and overall sexual satisfaction were found significantly impaired post-operatively. Sexual desire and frequency of attempted sexual intercourses were found significantly increased post-operatively, in comparison with pre-operative levels. With regard to patients' subjective perception on sexual functioning alterations after PC-RPLND, a significant number of patients reported higher levels of sexual desire, no difference in erectile function and worse orgasmic function and satisfaction post-operatively. Thus, patients subjected to PC-RPLND should be closely and routinely evaluated due to close relationship of sexual dissatisfaction with secondary psychological disorders.
Asunto(s)
Eyaculación , Disfunción Eréctil/etiología , Escisión del Ganglio Linfático/efectos adversos , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Testiculares/cirugía , Adulto , Antineoplásicos/uso terapéutico , Coito/psicología , Terapia Combinada , Disfunción Eréctil/psicología , Grecia , Humanos , Escisión del Ganglio Linfático/métodos , Escisión del Ganglio Linfático/psicología , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Orgasmo , Estudios Prospectivos , Espacio Retroperitoneal , Encuestas y Cuestionarios , Neoplasias Testiculares/tratamiento farmacológico , Adulto JovenRESUMEN
One presumed drawback of performing fluorescence in situ hybridization on routine tissue sections for HER-2 status evaluation in breast carcinomas is nuclear truncation. Therefore, HER-2/CEP 17 ratios were compared in routine (4 µm) vs. thicker (15 µm) tissue sections. Additionally, the distances of both signals from the nuclear center were measured by three-dimensional image analysis. HER-2 and CEP 17 signals' number increased in thick sections; however, HER-2/CEP 17 ratios were decreased. This could be attributed to a preferential increase in CEP17 signals explained by their more peripheral localization and apparent "loss" in truncated nuclei. The aforementioned decrease of HER-2 ratios did not alter HER-2 status except in cases in the equivocal category where it changed from equivocal to non-amplified. Thus, at least a subset of the equivocal cases could represent an artifactual increase of HER-2 ratio related to nuclear truncation and loss of peripheral CEP 17 signals in routine sections.
Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Cromosomas Humanos Par 17/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Femenino , Humanos , Hibridación Fluorescente in Situ , Microscopía Confocal , Transducción de SeñalRESUMEN
BACKGROUND: High expression of the actin-bundling protein fascin correlates well with histological grade and clinical stage of ovarian carcinoma. This study addresses fascin expression in advanced poorly differentiated serous ovarian cancer with respect to progression free interval (PFI) and overall survival. PATIENTS AND METHODS: Fascin and Ki-67 expression were analysed in paraffin blocks tissue sections of 56 stage III, poorly differentiated (G3) serous adenocarcinoma patients by immunohistochemistry. Fascin expression was tested for correlation with PFI and overall survival. RESULTS: Fascin expression inversely correlated with Ki-67 expression (p=0.016). Strong fascin immunoreactivity was associated with poor prognosis; patients with low fascin expression had a median survival of 36.5 months versus 32 months for high fascin expression (p=0.041), and the median PFI was 24 versus 17.5 months (p=0.034). CONCLUSION: Fascin expression is an independent prognostic factor for survival of advanced ovarian serous carcinoma, and may represent a novel therapeutic target for patients with aggressive forms of ovarian cancer.
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Proteínas Portadoras/biosíntesis , Proteínas de Microfilamentos/biosíntesis , Neoplasias Ováricas/metabolismo , Procesos de Crecimiento Celular/fisiología , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/biosíntesis , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patologíaRESUMEN
Only about half of patients with a poor-prognosis non-seminomatous germ-cell tumours can achieve a cure. The aim of this phase II study was to assess the efficacy and toxicity of a dose-dense alternating chemotherapy regimen in this subset of patients. High volume non-seminomatous germ-cell tumours was defined as follows: at least two sites of non pulmonary metastases, an extragonadal primary tumour, a serum human chorionic gonadotropin level higher than 10 000 mIU x ml(-1), or a alpha-foetoprotein level higher than 2000 mIU ml(-1). Patients who fulfilled these criteria were treated with the so-called BOP-CISCA-POMB-ACE regimen (bleomycin, vincristine, and cisplatin; cisplatin, cyclophosphamide, and doxorubicin; cisplatin, vincristine, methotrexate, and bleomycin; etoposide, dactinomycin, and cyclophosphamide) plus granulocyte colony-stimulating factor. A total of 58 patients were enrolled. Patients were retrospectively classified according to the International Germ-Cell Cancer Consensus Group classification; 38 patients (66%) had poor-prognosis disease and 19 patients (33%) had intermediate-prognosis. Patients received a median of 2.5 courses (range 0.25 to five courses) of the BOP-CISCA-POMB-ACE regimen. Forty-two patients (72.4%) had a complete response to therapy. With a median follow-up time of 31 months, the 3-year progression-free survival rate was 71% (95% confidence interval, 60 to 84%) and the 3-year overall survival rate was 73% (95% confidence interval: 62 to 86%). The 3-year PFS rates were 83% (95% confidence interval: 68 to 100%) in the intermediate-prognosis group and 65% (95% confidence interval: 51 to 82%) in the poor-prognosis group. Early side effects included mainly grade 4 haematologic toxicity (neutropaenia in 79% of patients, thrombocytopaenia in 69%, anaemia in 22%), grade 4 stomatitis (19%), and four early deaths (7% of patients), at least partially related to toxicity. The dose-dense BOP-CISCA-POMB-ACE regimen is highly active in patients with non-seminomatous germ-cell tumours classified as intermediate-prognosis or poor-prognosis according to the International Germ-Cell Cancer Consensus Group. Because outcomes with this regimen compare favourably with outcome after standard therapy, dose-dense chemotherapy should be further investigated in this subset of patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Germinoma/tratamiento farmacológico , Seminoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Adolescente , Adulto , Anemia Refractaria con Exceso de Blastos/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/sangre , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dactinomicina/administración & dosificación , Dactinomicina/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Germinoma/mortalidad , Germinoma/patología , Germinoma/secundario , Enfermedades Hematológicas/inducido químicamente , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Seminoma/mortalidad , Seminoma/patología , Seminoma/secundario , Análisis de Supervivencia , Tasa de Supervivencia , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/patología , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Clinical and laboratory observations support the view that angiogenesis is necessary for prostate cancer progression. The angiogenesis inhibitor TNP-470 has demonstrated in vivo antitumor activity in a series of clinical models. To evaluate a possible therapeutic clinical value, we conducted a Phase I dose escalation trial of alternate-day i.v. TNP-470 in 33 patients with metastatic and androgen-independent prostate cancer. The patients were evaluated during therapy for evidence of neurological toxic effects. An assay of endothelial and vascular proliferation "markers" and a sequential assay of serum prostate-specific antigen concentration were performed. The effects of TNP-470 could be evaluated in 32 of the 33 patients. The maximum tolerated dose was 70.88 mg/m(2) of body surface area. The dose-limiting toxic effect was a characteristic neuropsychiatric symptom complex (anesthesia, gait disturbance, and agitation) that resolved upon cessation of therapy. The times to clinical recovery of neurological side effects were 6, 8, and 14 weeks. No definite antitumor activity of TNP-470 was observed; however, transient stimulation of the serum prostate-specific antigen concentration occurred in some of the patients treated. Additional studies of TNP-470 should be conducted using an alternate-day i.v. injection of 47.25 mg/m(2) body surface area and should focus on understanding and overcoming the neurological toxic effects. In addition, valid intermediate end points that reflect the status of tumor-associated neovascularity are needed to facilitate effective development of treatment strategies.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Sesquiterpenos/uso terapéutico , Anciano , Andrógenos/metabolismo , Inhibidores de la Angiogénesis/efectos adversos , Glucemia/efectos de los fármacos , Huesos/efectos de los fármacos , Enfermedades Transmisibles/etiología , Ciclohexanos , Sistema Digestivo/efectos de los fármacos , Factores de Crecimiento de Fibroblastos/orina , Humanos , Cinética , Hígado/efectos de los fármacos , Masculino , Persona de Mediana Edad , O-(Cloroacetilcarbamoil) Fumagilol , Dolor/etiología , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/metabolismo , Sesquiterpenos/efectos adversos , Trombomodulina/sangreRESUMEN
BACKGROUND: Prostate carcinoma is linked to osteoblastic metastasis. We therefore investigated the value of bone-targeted consolidation therapy in selected patients with advanced androgen-independent carcinoma of the prostate. METHODS: 103 patients received induction chemotherapy, consisting of ketoconazole and doxorubicin alternating with estramustine and vinblastine. After two or three cycles of induction chemotherapy, we randomly assigned 72 patients who were clinically stable or responders to receive doxorubicin with or without strontium-89 (Sr-89) every week for 6 weeks. FINDINGS: Overall 62 of the 103 (60%, 95% CI 50-70) patients had a 50% or greater reduction in serum prostate-specific antigen concentration that was maintained for at least 8 weeks, and 43 (42%, 32-52) had an 80% or greater reduction. 49 (52%) patients with bone pain at registration had complete resolution of pain. After follow-up of 67 patients until death, the estimated median survival for all 103 patients was 17.5 months (range 0.5-37.7). For the 36 patients randomly assigned to receive Sr-89 and doxorubicin, the median survival time was 27.7 months (4.9-37.7), and for the 36 who received doxorubicin alone it was 16.8 months (4.4-34.2) (p=0.0014). The hazard ratio was 2.76 (95% CI 1.44-5.29). INTERPRETATION: Bone-targeted consolidation therapy consisting of one dose of Sr-89 plus doxorubicin once a week for 6 weeks, when given to patients with stable or responding advanced androgen-independent carcinoma of the prostate after induction chemotherapy, improved overall survival.
Asunto(s)
Neoplasias Óseas/prevención & control , Neoplasias Óseas/secundario , Carcinoma/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Radioisótopos de Estroncio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Neoplasias Óseas/mortalidad , Carcinoma/mortalidad , Doxorrubicina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Análisis de Supervivencia , Texas/epidemiologíaRESUMEN
BACKGROUND: Patients with metastatic renal cell carcinoma have a poor prognosis and no standard therapy is available. The authors performed a Phase II trial of the novel agent bryostatin-1 in this patient population. METHODS: In all, 30 patients with measurable, previously untreated metastatic renal cell carcinoma were studied. Patients had excellent physiologic reserve and preserved performance status. Bryostatin-1 (25 microg/m(2)) was given in the PET (polyethyleneglycol, ethanol, and Tween 80) formulation as a 30-minute intravenous infusion on Days 1, 8, and 15 of each 28-day cycle. In general, treatment was continued until disease progression. RESULTS: Two patients had significant objective responses, although methodologic problems made interpretation difficult. The median time to progression for all patients was 2.1 months; the median overall survival was 13.1 months. The treatment was generally well tolerated. Myalgia was the most common adverse event. One patient died while on study. This was a sudden death for a patient receiving a 15th cycle of therapy. Aside from this patient (for whom the correlation of study drug to death was not clear), no Grade 4 nonhematologic toxicity was encountered in more than 150 treatment courses delivered. CONCLUSIONS: There is minimal, if any, clinically relevant single-agent activity of bryostatin-1 at this dose and schedule for patients with metastatic renal cell carcinoma.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Lactonas/uso terapéutico , Adulto , Anciano , Brioestatinas , Carcinoma de Células Renales/secundario , Femenino , Humanos , Neoplasias Renales/patología , Macrólidos , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
This prospective Phase II study assesses the clinical efficacy and complications of a treatment regimen of combination chemotherapy with cyclophosphamide and carboplatin and selective consolidation in advanced seminoma. Of 46 patients who entered the study between December 1992 and October 1998, 46 were evaluable. Thirty-two achieved a complete remission (70%; 95% confidence interval, 56-83%) after chemotherapy alone. Fourteen achieved a complete remission (30%; 95% confidence interval, 18-46%) after chemotherapy plus consolidation. Forty-three of the 46 patients (93%; 95% confidence interval, 82-97%) remained in remission after a median follow-up period of 27.4 months. No patient experienced nephrotoxic, neurotoxic, or ototoxic effects or hemorrhagic cystitis. No patient had neutropenic fever requiring hospitalization. Thirteen % required platelet transfusions, and 9% required transfusions of packed RBCs. For patients with advanced seminoma, treatment with cyclophosphamide and carboplatin and selective consolidation is safe and effective.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Seminoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Carboplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Humanos , Masculino , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias del Mediastino/secundario , Persona de Mediana Edad , Glándula Pineal , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/secundario , Seminoma/mortalidad , Seminoma/secundario , Análisis de Supervivencia , Neoplasias Testiculares/mortalidad , Factores de TiempoRESUMEN
Angiogenesis is essential to prostate cancer progression. The first study of antiangiogenic therapy in patients with locally advanced prostate cancer at The University of Texas M. D. Anderson Cancer Center showed that preoperative treatment with a fumagillin analog was safe. Microvascular density correlated with Gleason score, but marked intertumoral and intratumoral changes were observed. Clinical experience with thalidomide (Thalomid), which inhibits angiogenesis induced by both vascular endothelial growth factor and basic fibroblast growth factor, has included observation of "clinical improvement" in patients with androgen-independent prostate cancer and anecdotal responses in patients with metastatic disease refractory to chemotherapy. In an effort to assess the in vivo effect of thalidomide in prostate carcinoma, we have initiated a study of neoadjuvant thalidomide treatment in patients with locally advanced prostate cancer that is to include serial ultrasonographic and pathologic evaluation, as well as serial collection of serum/urine markers that may prove useful surrogate markers of antiangiogenic activity. We have also initiated a phase I/II trial of thalidomide, paclitaxel (Taxol), and estramustine (Emcyt) in patients with metastatic androgen-independent prostate cancer progressing after up to two courses of chemotherapy.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Quimioterapia Adyuvante , Estramustina/uso terapéutico , Humanos , Masculino , Microcirculación/efectos de los fármacos , Paclitaxel/uso terapéuticoRESUMEN
PURPOSE: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. RESULT: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. CONCLUSION: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.
Asunto(s)
Ensayos Clínicos Fase II como Asunto/normas , Consensus Development Conferences, NIH as Topic , Selección de Paciente , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Andrógenos/metabolismo , Guías como Asunto , Humanos , Masculino , Neoplasias de la Próstata/terapia , Valores de Referencia , Estados UnidosRESUMEN
Prostate cancer (PCa) remains the most common cancer and the second leading cause of cancer mortality in men in the United States. The evolution from a localized to a metastatic phenotype coupled with the progression from an androgen-dependent (AD) to an androgen-independent (AI) state leads to a universally fatal disease. Identifying the biologic characteristics associated with PCa progression is a major goal of current research efforts by different groups, in the hope to better predict the natural history of the disease in an individual patient and to design treatments based on the specific biologic behavior.
Asunto(s)
Antígenos de Superficie , Biomarcadores de Tumor , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias de la Próstata/metabolismo , Antígenos de Neoplasias/metabolismo , Carboxipeptidasas/metabolismo , Citocinas/metabolismo , Progresión de la Enfermedad , Genes Supresores de Tumor , Glutamato Carboxipeptidasa II , Sustancias de Crecimiento/metabolismo , Humanos , Masculino , Neoplasias Hormono-Dependientes/genética , Neoplasias Hormono-Dependientes/fisiopatología , Sistemas Neurosecretores/metabolismo , Oncogenes , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/fisiopatología , Receptores Androgénicos/metabolismoRESUMEN
We have previously shown that Interferon-Inducible Protein-10 (IP-10), a cytokine chemotactic for CD4-positive lymphocytes, is overexpressed by lesional epidermal keratinocytes and probably accounts for the epidermotropism of cutaneous T-cell lymphoma (CTCL). The tax gene of human T-lymphotropic virus-I (HTLV-I) immortalizes CD4-positive lymphocytes, induces IFN-gamma, and has been detected in patients with classical CTCL who are seronegative for HTLV-I. TNF-alpha is synergistic with IFN-gamma for the induction of IP-10. We therefore decided to define the presence of tax, IFN-gamma, TNF-alpha, and IP-10 in lesions of 19 adults with classical CTCL who were seronegative for HTLV-I. Lesional mRNAs for actin, TNF-alpha, IFN-gamma, and tax were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) amplification. In addition IP-10, TNF-alpha, and IFN-gamma were detected and localized with immunocytochemistry of frozen sections. In agreement with previous observations IP-10 was overexpressed in lesional keratinocytes of all 19 patients. By RT-PCR, mRNA for IFN-gamma was detected in lesions of 8, and for TNF-alpha in lesions of 13 patients. By immunocytochemistry, TNF-alpha was expressed by lesional keratinocytes in 10 of 13 tested patients, whereas IFN-gamma was focally expressed by lesional lymphocytes and faintly by lesional keratinocytes in 9 of 13 tested patients. tax mRNA was not detected in lesions of any patient, but was easily detectable in cutaneous lesions or peripheral blood of control patients who were seropositive for HTLV-I. We conclude that TNF-alpha and IFN-gamma may cause epidermotropism by inducing IP-10. However, the tax gene of HTLV-I does not appear to be involved in the pathogenesis of classical CTCL.
Asunto(s)
Quimiocinas CXC/análisis , Productos del Gen tax/análisis , Interferón gamma/análisis , Linfoma Cutáneo de Células T/química , Proteínas de Neoplasias/análisis , Factor de Necrosis Tumoral alfa/análisis , Adulto , Anciano , Anciano de 80 o más Años , Quimiocina CXCL10 , Femenino , Humanos , Masculino , Persona de Mediana Edad , TropismoRESUMEN
Because the outcome of patients with primary ovarian non-Hodgkin's lymphoma (NHL) is controversial, we retrospectively analyzed experience with adults seen at the University of Texas M. D. Anderson Cancer Center from 1974 to 1993. Patients were included if at least one ovary was pathologically involved, and if combination chemotherapy was used that must have included doxorubicin for intermediate grade histologies. We identified 15 patients who constituted 0.5% of all untreated NHL and 1.5% of untreated ovarian neoplasms that presented to our instutition during this time. One patient refused therapy, leaving 14 assessable for response. Nine patients had intermediate-grade, 5 had high-grade, and none had low-grade NHL. One ovary was involved in 4 patients, and both in 10, in 7 of whom additional sites were involved, including supradiaphragmatic nodes in 2. Four patients had AAS I and 10 had AAS IV. Favorable (0 or 1) and unfavorable (>1) IPI scores were seen in 5 and 9 patients, respectively. The complete remission rate for all patients was 64%, and 5-year survival and FFS for all assessable patients were 57 and 46%, respectively. We conclude that the complete remission rate and FFS of patients with ovarian NHL treated with appropriate chemotherapy appear to be similar to that of patients with other nodal NHLs. Further work is required to determine prognostic factors in ovarian NHL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Linfoma no Hodgkin/mortalidad , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Human IFN-gamma-inducible protein 10 (IP-10), a C-X-C chemokine secreted by IFN-gamma-stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits the proliferation of early subsets of normal and of leukemic hemopoietic progenitors. Cutaneous T-cell lymphoma (CTCL) is an indolent lymphoproliferative disorder of CD4-positive lymphocytes that remain confined to the skin for many years before visceral dissemination. Because IFN-gamma mRNA was detected in the epidermis of CTCL lesions, we decided to investigate the role of IP-10 in the epidermotropism of CTCL by determining its expression in normal skin and in CTCL lesions. Using purified recombinant IP-10 (rIP-10) or a recombinant fusion protein between IP-10 and the straight phi10 protein of phage T7, we generated rabbit antisera that recognized and neutralized rIP-10. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal keratinocytes but not by the more differentiated cells. In the often hyperplastic epidermis overlying CTCL lesions, IP-10 immunostaining was enhanced compared to normal skin and extended to the suprabasal keratinocytes in 28 of 29 patients for a frequency of 97% and a 95% confidence interval of 82-100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only 3 of 29 patients (10%; 95% confidence interval, 2-29%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was overexpressed before treatment but was normally expressed at remission. The in vitro proliferation of primary normal human keratinocytes was inhibited in a dose-dependent manner by rIP-10. These results suggest that IP-10 plays a role in the epidermotropism of CTCL. Additional work is needed to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be useful in the development of curative strategies for this disorder.
Asunto(s)
Quimiocinas CXC/fisiología , Interferón gamma/metabolismo , Linfoma Cutáneo de Células T/etiología , Neoplasias Cutáneas/etiología , Adulto , Anciano , Anciano de 80 o más Años , División Celular , Quimiocina CXCL10 , Quimiocinas CXC/biosíntesis , Citocinas/metabolismo , Femenino , Humanos , Queratinocitos/metabolismo , Queratinocitos/patología , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/patologíaRESUMEN
Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% Cl, 2% to 39%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.
Asunto(s)
Quimiocinas CXC/metabolismo , Queratinocitos/metabolismo , Linfoma Cutáneo de Células T/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Cutáneas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Quimiocina CXCL10 , Femenino , Humanos , Linfoma Cutáneo de Células T/etiología , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/etiologíaRESUMEN
Light chain deposition disease (LCDD) and light and heavy chain deposition disease (LHCDD) are rare clinical entities that have been associated with multiple myeloma, with monoclonal gammopathy of unknown significance (MGUS), or without any detectable protein abnormality. Renal failure is common, the diagnosis is difficult and prolonged survival is rare. The first patient with LHCDD and MGUS who progressed to multiple myeloma after 11 years is presented. A rising level of monoclonal IgA immunoglobulin, bone marrow plasmacytosis, and the presence of multiple bone marrow lesions on magnetic resonance imaging provided the first evidence of disease evolution. When management of serious complications permits a long survival, some patients with LCDD or LHCDD will develop multiple myeloma.
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Mieloma Múltiple/etiología , Paraproteinemias/complicaciones , Membrana Basal/inmunología , Membrana Basal/patología , Médula Ósea/patología , Mesangio Glomerular/inmunología , Mesangio Glomerular/patología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina A/orina , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Imagen por Resonancia Magnética , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Mieloma Múltiple/patología , Paraproteinemias/inmunología , Columna Vertebral/patologíaAsunto(s)
Anemia Hemolítica Autoinmune/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anemia Hemolítica Autoinmune/etiología , Antineoplásicos/uso terapéutico , Cladribina/uso terapéutico , Humanos , Inmunoglobulina M/sangre , Linfoma de Células B/complicaciones , Linfoma de Células B Grandes Difuso/inmunologíaRESUMEN
The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated activity in colorectal cancer (CC). Cisplatin is reported to have synergistic activity with 5-FU. We examined the combination FA + 5-FU + cisplatin in patients who had previously received chemotherapy with FA + 5-FU and relapsed. Two months after the last dose of FA + 5-FU and documentation of relapse, patients continued with the regimen consisting of cisplatin 20 mg/m2 in 15 min i.v. infusion followed by FA 500 mg/m2 in 1 h i.v. infusion, in the middle of which 5-FU 500 mg/m2 i.v. bolus was administered, with adequate post-hydration. This was repeated weekly for 4 weeks followed by a 2 week rest, for a maximum of six cycles. A total of 30 patients with CC that had relapsed to the combination of FA + 5-FU were treated; 23 had previous surgery and none had radiotherapy. Local recurrence was found in eight patients, metastases in the liver in 21, in lymph nodes in six, lung six and peritoneal metastases in seven. Seven patients responded partially. Toxicity requiring dose reduction or discontinuation of treatment included neutropenia 42% (grade 3:7%), mucositis 28% (grade 1:2), diarrhea 63% (Grade 3:10%), nausea-vomiting 55% (Grade 3:10%), increased creatinine value in three patients and peripheral neuropathy in two patients. We conclude that evaluation of this regimen shows substantial toxicity, with satisfactory response as a second line chemotherapy in these heavily pretreated patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recuento de Células Sanguíneas , Cisplatino/administración & dosificación , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Proyectos Piloto , RecurrenciaRESUMEN
The purpose of this study was to determine whether preloading administration of ondansetron given 12.5 h before cisplatin therapy, every 6 h, is better in controlling acute cisplatin-induced emesis than a standard dose every 8 h. All patients had previously received three cycles of CDDP-based chemotherapy in a dose of 100 mg/m2. Ondansetron was given according to two schedules: in group A (40 patients) at a dose of 8 mg in 100 ml normal saline over 10 min by intravenous infusion before the infusion of CDDP continued with 1 tablet of 8 mg after 8 and 16 h; in group B (40 patients) it was administered in six intravenous doses (every 6 h) starting 12.5 h before cisplatin administration. During the following 3 days, patients from both groups continued with tablets of 8 mg orally, every 8 h in group A and every 6 h in group B. The only difference in terms of the antiemetic response noticed between the two groups was in the number of patients that presented with nausea, which was increased in group A (32) in comparison to group B (25; p < 0.022). No difference was found in the number of vomiting episodes, retches or control of emesis, during the 3-day evaluation period after cisplatin infusion, and in secondary side effects. In conclusion the total dose of 24 mg ondansetron during the acute phase of emesis is as effective as preloading and increasing the total dose to 32 mg.
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Ondansetrón/administración & dosificación , Premedicación , Vómitos/prevención & control , Adulto , Anciano , Cisplatino/efectos adversos , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/prevención & control , Vómitos/inducido químicamenteRESUMEN
The therapeutic benefit of chemotherapy in androgen independent prostate cancer is limited. 5-Fluorouracil has been reported to have modest antitumor activity in androgen independent prostate cancer. Although alpha-interferon is inactive as a single agent in prostate cancer, preclinical data indicate that it increases the in vitro cytotoxicity of 5-fluorouracil against a variety of malignant cells. We evaluated the relative antitumor activity and tolerance of 5-fluorouracil versus 5-fluorouracil plus alpha-interferon in 50 patients with histologically confirmed metastatic adenocarcinoma of the prostate. These patients had progressive disease in the presence of castrate levels of testosterone. A prospective randomized phase II open labeled trial was performed because of the difficulty in measuring responses in patients with metastatic prostate cancer. Of 23 patients treated with 5-fluorouracil alone and 28 treated with 5-fluorouracil plus alpha-interferon 17 and 23, respectively, were evaluable for response and toxicity, and 5 and 5, respectively, were evaluable for toxicity only. Only 2 of 17 (11.7%) and 4 of 23 (17%) patients, respectively, showed a greater than 50% decrease in serum prostate specific antigen (no significant difference). There was no difference in duration of response or duration of survival between the 2 groups (mean duration of response 8.64 and 6.17 weeks, respectively, and mean duration of survival 33.70 and 38.65 weeks, respectively). Both regimens caused significant morbidity (mucositis and neurotoxicity) and 3 treatment related deaths at the high 5-fluorouracil doses. 5-Fluorouracil alone and with alpha-interferon at the doses used have minimal antitumor activity against androgen independent prostate cancer and, therefore, should not be tested further in these patients. Androgen independent prostate cancer selected using our criteria is a rapidly progressive disease, and these patients are an ideal target population for phase II studies.