Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells.

Resveratrol, a plant antibiotic, has been found to have anticancer activity and was recently reported to induce apoptosis in the myeloid leukemia line HL60 by the CD95-CD95 ligand pathway. However, many acute lymphoblastic leukemias (ALLs), particularly of B-lineage, are resistant to CD95-mediated apoptosis. Using leukemia lines derived from patients with pro-B t(4;11), pre-B, and T-cell ALL, we show in this report that resveratrol induces extensive apoptotic cell death not only in CD95-sensitive leukemia lines, but also in B-lineage leukemic cells that are resistant to CD95-signaling. Multiple dose treatments of the leukemic cells with 50 microM resveratrol resulted in >/=80% cell death with no statistically significant cytotoxicity against normal peripheral blood mononuclear cells under identical conditions. Resveratrol treatment did not increase CD95 expression or trigger sensitivity to CD95-mediated apoptosis in the ALL lines. Inhibition of CD95-signaling with a CD95-specific antagonistic antibody indicated that CD95-CD95 ligand interactions were not involved in initiating resveratrol-induced apoptosis. However, in each ALL line, resveratrol induced progressive loss of mitochondrial membrane potential as measured by the dual emission pattern of the mitochondria-selective dye JC-1. The broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone failed to block the depolarization of mitochondrial membranes induced by resveratrol, further indicating that resveratrol action was independent of upstream caspase-8 activation via receptor ligation. However, increases in caspase-9 activity ranged from 4- to 9-fold in the eight cell lines after treatment with resveratrol. Taken together, these results point to a general mechanism of apoptosis induction by resveratrol in ALL cells that involves a mitochondria/caspase-9-specific pathway for the activation of the caspase cascade and is independent of CD95-signaling.

Localization, implications for function, and gene expression of chymotrypsin-like proteinases of cytotoxic RNK-16 lymphocytes.

Rat RNK-16 leukemia cells kill YAC-1, which are the cells lysed by rodent natural killer lymphocytes. We found chymotrypsin-like proteinase ('chymase') activity in the RNK-16 dense granules that also contain cytolytic activity. The chymase activity hydrolyzed the thiobenzyl peptide substrate Suc-Phe-Leu-Phe-SBzl and, in comparison to RNK-16 tryptase activity, was selectively inhibited by three different types of serine proteinase inhibitors. The selective inhibitors were the fungal aldehyde chymostatin, the chloromethylketone Z-Gly-Leu-Phe-CH2Cl, and the mechanism-based or 'suicide' inhibitor 7-amino-4-chloro-3-(2-phenylethoxy)isocoumarin. These proteinase inhibitors also blocked RNK-16 granule-mediated cytolysis. Chymostatin, a reversible inhibitor, delayed granule-mediated cytolysis, whereas the irreversible chloromethylketone and isocoumarin proteinase inhibitors completely abrogated granule-mediated cytolysis. The two irreversible inhibitors displayed biphasic inhibition of the chymase activity, indicating that at least two chymases are present in the granules. By Northern blot analysis, we found that RNK-16 mRNA hybridized strongly with a cDNA probe of CCPI, a mouse cytotoxic T lymphocyte serine proteinase gene. These data imply that chymase activity in the cytotoxic granules is important for cytolytic function and is likely to belong to a new subfamily of serine proteinases.

Regulation of CD95 expression and CD95-mediated cell death by interferon-gamma in acute lymphoblastic leukemia with chromosomal translocation t(4;11).

The regulatory effects of IFNgamma on CD95 expression and CD95-mediated cell death were investigated in three high-risk pro-B acute lymphoblastic leukemia (ALL) lines that carry the chromosomal translocation t(4;11)(q21;q23). These leukemias are characteristically refractory to conventional chemotherapeutic treatments operating through the induction of apoptosis. However, the mechanisms leading to increased cell survival and resistance to cell death in these leukemias are largely unknown. Interferon-gamma (IFNgamma), a potent inhibitor of hematopoiesis, acts in part by upregulating CD95 and sensitizing cells to CD95-induced apoptosis. The t(4;11) lines SEM, RS4;11, and MV4;11 expressed low levels of CD95, but were completely resistant to CD95-mediated death. Addition of IFNgamma markedly upregulated CD95 expression in SEM (8-9-fold), RS4;11 (2-3-fold), and MV4;11 (2-3-fold) lines. However, after treatment with IFNgamma, only an 11% increase in sensitivity to CD95-mediated cell death was observed in SEM cells, whereas RS4;11 and MV4;11 cells remained resistant. Cycloheximide, but not actinomycin D or brefeldin A, increased CD95-specific cell death only in IFNgamma-treated RS4;11 cells by approximately 12%. Abundant levels of Bcl-2 and Bcl-XL, known to inhibit CD95-signaling in some cells, were present suggesting a possible role for both molecules in the resistance to CD95-mediated cell death. Resistance of the leukemic blasts to CD95-mediated cell death and the failure of IFNgamma to substantially sensitize the CD95-signaling pathway may contribute to the highly malignant phenotype of pro-B ALL with translocation t(4;11).

An improved procedure for the generation of recombinant single-chain Fv antibody fragments reacting with human CD13 on intact cells.

A procedure was developed to generate recombinant single chain Fv (scFv) antibody fragments reacting with the extracellular domain of human cell surface antigen CD13 (hCD13; aminopeptidase N) on intact cells. Membrane fractions prepared from a stably transfected hCD13-positive murine NIH/3T3 cell line were used to immunize BALB/c mice, with the intention that hCD13 would be the major immunogenic molecule recognized by the immune system. Spleen RNA from the immunized mice served to generate a combinatorial scFv phage display library. The library was adsorbed against non-transfected NIH/3T3 or Sf21 insect cells to eliminate nonrelevant binders. The supernatant was then used for panning with either hCD13-transfected Sf21 insect cells or a hCD13-expressing human leukemia-derived cell line. Therefore, the key concepts of the procedure were the presentation of hCD13 as the sole human antigen on murine NIH/3T3 cells and a screening strategy where hCD13 was the major common antigen of the material used for immunization and panning. Two different hCD13-reactive phages were isolated and the soluble scFvs were expressed in E. coli and purified. The two scFvs, anti-hCD13-1 and anti-hCD13-3, differed at four amino acid positions in their V(H) regions and both had high affinities for hCD13 as determined by surface plasmon resonance (K(D)=7 and 33x10(-10) M, respectively). Both efficiently recognized hCD13 on intact cells. Therefore, the procedure allowed the production of high affinity scFvs reacting with a desired antigen in its native conformation without requiring extensive purification of the antigen and should be useful for the preparation of scFvs against other conformation-sensitive cell-surface antigens.

Anatomic study of the pelvis in carcinoma of the uterine cervix as related to the box technique.

PURPOSE: To review the radiation therapy "box" technique for cancer of the cervix by means of magnetic resonance imaging (MRI), lymphangiography, and anatomic studies on cadavers. METHODS AND MATERIALS: From 1993 to 1996, the anatomic borders of the "box" technique used at our Radiation Oncology Department-the superior border of the AP-PA fields at the inferior edge of L4; the inferior border at the inferior edge of the ischium; the lateral borders placed 2.5 cm outside of the bony pelvis rim; the anterior border of the lateral fields over the anterior edge of the pubic symphysis; and the posterior at the S2-S3 interspace-were reviewed in 35 sagittal MRI and 10 lymphangiographies of patients with FIGO IB (6), IIA (6), IIB (19), IIIB (3), and IVA (1). An anatomic revision was conducted on 30 cadavers to identify aortic bifurcation, lymphatic nodes, and uterus flexion. RESULTS: In 50% of the patients with FIGO IB, the posterior border of the lateral field was inadequate to encompass the planning target volume (PTV), and in 67% with Stage IIA. In IIB, the anterior border was inadequate in 1 patient, and the posterior in 8 (42%). In IIB and IVA patients, the PTV was not encompassed. When correlating the anterior and posterior borders of the lateral field and the treatment volume in the 35 sagittal MRIs, the posterior border of the lateral field was inadequate in 49%, and the anterior border in 9% of the cases. According to the lymphangiography, the portals encompassed the external iliac nodes. Dissected female pelvises revealed that the aortic bifurcation occurred at the level of the inferior L4 edge in 80% of the cadavers. There was no correlation between uterus flexion in MRIs and in cadavers. CONCLUSION: The design of the lateral fields of the four-field technique for the irradiation of the uterine cervix based on anatomic bone references failed to encompass the planning-target volume in a significant number of patients.

Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia cells.

Carnosol, a phenolic compound extracted from the herb rosemary has been reported to have anti-cancer activity. We investigated whether carnosol was cytotoxic against several pro-B and pre-B acute lymphoblastic leukemia (ALL) lines. In all ALL lines tested, carnosol induced apoptotic cell death distinguished by loss of nuclear DNA, externalization of cell membrane phosphatidylserine, and depolarization of mitochondrial membranes. Flow cytometric measurement of Bcl-2 protein levels revealed that carnosol induced a 34-53% decrease in Bcl-2 in the cell population exhibiting a viable phenotype prior to detectable apoptotic changes in morphology. These results suggest that carnosol may be useful as a novel chemotherapeutic agent against B-lineage leukemias, and possibly other types of cancers that express high levels of the protective protein, Bcl-2.

[Radiation treatment in advanced cancer of the lung]. / Tratamiento radiante en cáncer avanzado de pulmón.

This is an attempt to evaluate the results of the radiotherapeutic treatment in patients with advanced lung cancer. The results of a series of 200 patients with lung cancer no oat cell. Average age: 59 years, ranging from 39 to 78, with male frank predominance (174/200). The histologic diagnosis was obtained in 159/200 (79.5%) of the patients of which, 52.8% were epidermoid carcinomas. The series was classified in three staging according to the American Joint Committee for Cancer Staging and End Results Reporting (AJC); the results was: 172/100 (86%) E III and 28/200 (14%) E I and II. The main objective of this work was the anlysis of E III which was subdivided into E III M0 and E III M1 for its study according to the absence or presence of metastasis when making the diagnosis. Besides, the patients were classified according to their clinical state at the beginning of treatment (performance status) following the Zubrod's scales. The statistics analysis shows the prognostic relevance of this parameter. The results of the two plans of irradiation treatment were analysed: continuous cycle (60 Gy in 6 weeks) and split course (2 cycles of 30 Gy in two weeks with three weeks of rest in between). There were not statisticaly significant difference either in the clinical or in the radiological response in both groups. Both groups were correlated under the following parameters: a) Performance Status, b) immediate response to treatment, c) quality of life after radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Interstitial implant with Au198 in prostatic cancer]. / Implantes intersticiales con Au198 en cáncer prostático.

Since 1983 to 1987, 13 patients with prostate cancer have been treated. The average age was 64.5 years. All of them were staged according to Whitmore and Jewett systems. Patients with B1, B2, C1 and C2 staging were included in this work. To evaluate the regional nodes, the patients underwent pelvic lymphadenectomy. Interstitial Au198 was performed at the time of operation. The interstitial irradiation delivered to the prostate was of 40 Gy and it was supplemented with CO60 (external beam therapy) till an equivalent of 60 Gy. When the lymphatic nodes were involved, the whole pelvic, ganglionic chain was irradiated. The results achieved with combined treatment of Au198 plus external beam therapy were the reduction of the prostate size, the disappearance of urinary symptoms and the complementary evaluation was normal for the 13 patients. Three out of 11 patients showed bone metastases in the follow up. One of them had also local relapse. Complications associated to radiotherapy were mild to moderate. Only one of the patients required diverting colostomy but he had suffered from rectal disease before radiotherapy. The results achieved until the close of this first report can be considered satisfactory if tumor regression and local control are taken into account, but the average time of follow up is too short to evaluate the survival rate.

Management of child optic pathway gliomas: new therapeutical option.

OBJECTIVE: To present our experience in the treatment of child optic pathway gliomas in the last 25 years. MATERIAL AND METHODS: Seventeen children under 10 years of age have been analyzed and assessed from clinic, ophthalmologic, endocrinologic, neurological, neuropathologic, and imaginologic points of view. RESULTS: Predominance of female patients, 10 girls and 7 boys between 6 and 122 months old; mean age was 3 years and 8 months. The most frequent symptoms have been ophthalmologic and visual alterations in all 17 patients, endocrine alterations in 10, and neurological signs in 6. One of the patients presented neurofibromatosis type 1 (NF1), another patient had Down syndrome. Diagnosed using computed tomography or/and magnetic resonance imaging, histological studies showed pilocytic astrocytomas in 13 cases and a fibrillary astrocytoma grade II in 1 case. There were three patients without histological diagnosis; one of them had NF1. The treatment consisted of surgery, external beam radiotherapy, chemotherapy, and brachytherapy with iodine 125, separately or combined. Five patients died; the causes were secondary tumors in two children, tumor recurrence in one, sepsis secondary to respiratory and urinary tract infections in the child with Down syndrome, and finally, hydrocephaly due to hyperproteinorachia of tumor origin in one. Average survival was 89 months. CONCLUSION: Chemotherapy and brachytherapy are therapeutic methods to be considered, especially in children under 5. Marsupialization of the residual cyst into the ventricular system postradio or oncolytic treatment through endoscopic or stereotactic techniques is useful in the treatment of endocranial hypertension and/or hypothalamic compression in these patients.

Interactions between human natural killer (NK) lymphocytes and yeast cells: human NK cells do not kill Candida albicans, although C. albicans blocks NK lysis of K562 cells.

Rodent natural killer (NK) lymphocytes are cytotoxic to certain fungi. We investigated whether human NK cells are cytotoxic to the yeast Candida albicans. We found that human peripheral blood lymphocytes possessing NK cell activity had little or no effect on the viability of the yeast. Unopsonized C. albicans, however, were able to block NK cell-mediated cytotoxicity at a ratio of 100 yeast to one K562 erythroleukemia cell. C. albicans was not toxic to the lymphocytes nor did it take up isotope released by the K562 cells. Furthermore, C. albicans that was pretreated with human serum blocked NK cell activity more than did untreated C. albicans. Binding of the yeasts to NK cells could account for the blocking effect of serum-treated yeasts, but not for that of the untreated yeasts. Flow cytometry indicated that there was preferential binding of C. albicans to NK lymphocytes but not to T cells when the yeasts were pretreated with human serum. In this report we affirm the results of the study by Vecchiarelli et al. (A. Vecchiarelli, F. Bistoni, E. Cenci, S. Perito, and A. Cassone, Sabouraudia 23:377-387, 1985), that the first report of rodent NK cell activity against the yeast Cryptococcus neoformans (J. W. Murphy and D. O. McDaniel, J. Immunol. 128:1577-1583, 1982) cannot be extrapolated to a general phenomenon of unprimed lymphocyte-mediated destruction of all species of yeast. Our data extend the observations to humans and also suggest that in vivo interactions between NK lymphocytes and opportunistic fungal pathogens may affect NK cell function.

RNKP-1, a novel natural killer-associated serine protease gene cloned from RNK-16 cytotoxic lymphocytes.

From an RNK-16 lambda-gt11 library, we have isolated and sequenced a novel cDNA rat NK cell protease 1 (RNKP-1) that has characteristics unique to serine proteases. The cDNA clone is 1102 bp and contains a complete open reading frame with an AUG start codon and a TAA stop codon. The open reading frame translates into a protein of 248 amino acids that has one glycosylation site. The characteristic N-terminal Ile-Ile-Gly-Gly and the His, Asp, and Ser amino acid residues that form the catalytic triad of serine proteases are present. The nucleotide and amino acid sequences have 87 and 80% identity, respectively, with the murine CTL-specific serine protease CCPI. However, there are extensive differences in the substrate binding regions of these proteases. Comparison of hydropathic profiles and amino acid sequences of other proteases indicate that RNKP-1 is distinct and belongs to the subfamily of serine proteases of bone marrow origin. Northern blot analysis of poly A+ RNA from rat splenocytes cultured with Con A showed 1000 and 1400 nucleotide mRNA are detected with RNKP-1 after 1 day of Con A-stimulation. The expression of the two mRNA bands continues through day 5 of culture with the lectin and may represent RNKP-1 mRNA plus related sequences due to cross-hybridization. RNKP-1 is also expressed in RNK-16 cells, but is not expressed in freshly isolated rat splenocytes, brain, lung, or lymph node tissues. The induction of RNKP-1 expression in the Con A-cultured spleen cells is accompanied by increases in both NK and lymphokine-activated killer lymphocyte activities. These data indicate that RNKP-1 is a unique serine protease that may be preferentially expressed in NK cells.

Interleukin-1 promotes hyperglycemia and insulitis in mice normally resistant to streptozotocin-induced diabetes.

By administering physiological doses of interleukin-1 (IL-1) concurrently with multiple low doses of the beta cell toxin streptozotocin (MSZ), we observed an augmentation of diabetes by IL-1 in four different strains of mice. Augmentation of hyperglycemia by IL-1 was most prominent in the two MSZ-resistant mouse strains Balb/cJ and A/J. Furthermore, concurrent treatment with IL-1 and MSZ rendered these MSZ-resistant mice susceptible to the development of significant insulitis when compared to mice treated with MSZ alone. Development of insulitis was dependent upon the dose of IL-1; it was only observed at an IL-1 dose of 250 ng/kg body weight. Analysis of the leukocytic infiltrate in the islets of mice after treatment with 250 ng/kg IL-1 plus MSZ revealed the presence of L3T4+ and Lyt-2+ T lymphocytes. Administration of MSZ alone or IL-1 alone did not produce diabetes in the MSZ-resistant mice, indicating that neither of these agents was toxic to the beta cells by itself. We conclude that IL-1 synergizes with MSZ to augment diabetes in mice that are normally resistant to the diabetogenic effects of MSZ.

Immunodetection of histone epitopes correlates with early stages of apoptosis in activated human peripheral T lymphocytes.

By coupling intracellular staining with terminal deoxynucleotidyl transferase (TdT)-mediated labeling of internucleosomal DNA strand breaks in a flow cytometric assay, we observed a strong correlation between apoptosis-associated DNA strand breaks and immunoreactivity with the monoclonal antibody (MAb) B-F6 in activated human peripheral blood T lymphocytes (PBTs). Although MAb B-F6 has been reported to be specific for the cytokine interleukin-6, Western blot analysis of activated PBT lysates revealed that the predominant protein band detected by this MAb was 17 kd (p17), distinct from the 23-kd core protein and 26- to 30-kd mature glycosylated forms of interleukin-6. Immunoaffinity isolation and amino-terminal amino acid sequence analysis of p17 revealed identity with the histone H2B, a finding confirmed by Western blot analysis of purified histones and by similar staining of activated PBTs with an unrelated anti-histone MAb. Neither histone staining nor DNA strand breakage was observed in freshly isolated PBTs; however, after T cell activation, histone immunoreactivity appeared to precede the appearance of DNA strand breaks, with both increasing to a maximal level by day 3 after activation. Two-parameter confocal immunofluorescence microscopy of histone and DNA staining confirmed a lack of histone immunoreactivity in viable cells and demonstrated co-localization of histone epitopes with abnormally clumped chromatin in apoptotic cells. These data indicate that alteration of histone epitope accessibility is a marker of early apoptosis and suggest that multiparameter flow cytometric analysis of intracellular epitopes may be a powerful tool in the elucidation of intracellular mechanisms of apoptosis.

Gliomas cerebrales de bajo grado en el adulto / Low grade gliomas un adults

Objetivo. Bajo esta denominación se incluyen a los astrocitomas fibrilares y protoplasmáticos, a los oligodendrogliomas, y a los oligoastrocitomas o tumores mixtos, que corresponden a los grados II de la nueva clasificación de la OMS . Los astrocitomas de bajo grado representan el 15% de los gliomas hemisféricos cerebrales en el adulto. Los oligodendrogliomas tienen una incidencia del 4% (2,4). Presentamos la experiencia de nuestro grupo de trabajo con este tipo de tumores entre enero de 1972 y diciembre de 2006.Material y método. Se analizaron las historias clínicas de 25 pacientes adultos que presentaron esta variedad de tumor, de los cuales 15 eran mujeres y 10 varones, que representan el 15,6% de los gliomas cerebrales en este grupo etario. Resultados: Quince eran astrocitomas fibrilares, ocho oligodendrogliomas y dos oligoastrocitomas. El principal estudio de imagen fue la resonancia nuclear magnética con espectroscopia. El tratamiento dependió de la ubicación y del volumen tumoral, siendo la cirugía y la radioterapia las modalidades terapéuticas mas empleadas. El tumor recidivó en 16 enfermos, con una media de 37 ± 21 meses después del diagnóstico, cuyas histopatologías mostraron ser: astrocitomas anaplásicos en 7 y glioblastomas multiformes en 9. Han fallecido 16 enfermos, 14 por el tumor cerebral, uno por cáncer de lengua y otro por embolia pulmonar producida a los 10 días de la cirugía, con una mediana de sobrevida de 44 meses (10 días a 120 meses). De los 9 pacientes que viven, 7 tienen oligodendrogliomas, 2 astrocitomas, y uno tiene un oligoastrocitoma; 7 requieren medicación antiepilética, ninguno tiene secuelas neurológicas, con una mediana de sobrevida de 36 meses (6 a 120 meses); dos han tenido recidiva, correspondientes a un oligodendroglioma y a un oligoastrocitoma, a los 22 y 60 meses respectivamente del diagnóstico, en los dos casos el tumor pasó de ser un grado II a grado III...

Objective. Gliomas reviewed in this article are grade II tumors according to the World Health Organization (WHO), that include: fibrillary and protoplasmic astrocytomas, oligodendrogliomas and oligoastrocytomas or mix tumors (1,2,3).Low grade astrocytomas constitute 15% of brain tumors in adults, while low grade oligodendrogliomas represent 4% (2,4). We present our experience with this type of tumor operated on between January 1972 and December 2006.Material and Method. The clinical reports of 25 patients with this type of tumor were analyzed, 15 women and 10 men, which represent 15,6% of hemispheric brain gliomas in adults in our series.Results. Fifteen were fibrillary astrocytomas, 8 oligodendrogliomasand 2 oligoastrocytomas. Treatment depended on tumor localization and size. Surgery and radiotherapy were thetherapeutic modalities most frequently used. Tumor recurrence was observed in 16 patients, with a media of 37+/- 21 months after diagnosis: 7 anaplastic astrocytomas and 9 glioblastomasmultiforme. In this series, 16 patients died with a median of 44 months (10 days to 120 months) after diagnosis. Cause of death were: tumor itself, in 14 cases, tongue cancer in 1, and pulmonaryembolism after surgery in another. From the 9 surviving patients, 6 have oligodendrogliomas, 2 astrocytomas and 1 an oligoastrocytoma. Seven patients need antiepileptic drug and none of them presents neurological sequels. The survival mediana was 36 months (6 to 120 months). Two of them had tworecurrences between 22 and 60 months after diagnosis, one oligodendroglioma and the other an oligoastrocytoma; in both cases tumors grade II became tumors grade III. Conclusion. The relative incidence of 15,6% in adult gliomas of our series is similar to the international experience. Age, younger as 40 years, seizures, as clinical presentation, extension of surgical resection, low Ki 67 index in astrocytomas, and...

Tratamiento radiante en cáncer avanzado de pulmón. / [Radiation treatment in advanced cancer of the lung]

This is an attempt to evaluate the results of the radiotherapeutic treatment in patients with advanced lung cancer. The results of a series of 200 patients with lung cancer no oat cell. Average age: 59 years, ranging from 39 to 78, with male frank predominance (174/200). The histologic diagnosis was obtained in 159/200 (79.5

) of the patients of which, 52.8

were epidermoid carcinomas. The series was classified in three staging according to the American Joint Committee for Cancer Staging and End Results Reporting (AJC); the results was: 172/100 (86

) E III and 28/200 (14

) E I and II. The main objective of this work was the anlysis of E III which was subdivided into E III M0 and E III M1 for its study according to the absence or presence of metastasis when making the diagnosis. Besides, the patients were classified according to their clinical state at the beginning of treatment (performance status) following the Zubrods scales. The statistics analysis shows the prognostic relevance of this parameter. The results of the two plans of irradiation treatment were analysed: continuous cycle (60 Gy in 6 weeks) and split course (2 cycles of 30 Gy in two weeks with three weeks of rest in between). There were not statisticaly significant difference either in the clinical or in the radiological response in both groups. Both groups were correlated under the following parameters: a) Performance Status, b) immediate response to treatment, c) quality of life after radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Implantes intersticiales con Au198 en cáncer prostático. / [Interstitial implant with Au198 in prostatic cancer]

Since 1983 to 1987, 13 patients with prostate cancer have been treated. The average age was 64.5 years. All of them were staged according to Whitmore and Jewett systems. Patients with B1, B2, C1 and C2 staging were included in this work. To evaluate the regional nodes, the patients underwent pelvic lymphadenectomy. Interstitial Au198 was performed at the time of operation. The interstitial irradiation delivered to the prostate was of 40 Gy and it was supplemented with CO60 (external beam therapy) till an equivalent of 60 Gy. When the lymphatic nodes were involved, the whole pelvic, ganglionic chain was irradiated. The results achieved with combined treatment of Au198 plus external beam therapy were the reduction of the prostate size, the disappearance of urinary symptoms and the complementary evaluation was normal for the 13 patients. Three out of 11 patients showed bone metastases in the follow up. One of them had also local relapse. Complications associated to radiotherapy were mild to moderate. Only one of the patients required diverting colostomy but he had suffered from rectal disease before radiotherapy. The results achieved until the close of this first report can be considered satisfactory if tumor regression and local control are taken into account, but the average time of follow up is too short to evaluate the survival rate.

Cáncer de mama estadios I y II: análisis retrospectivo de las recidivas en 834 pacientes tratadas con mastectomía o en forma conservadora / Breast cancer stage I and II: retrospective analysis of the recurrence in 834 patients treated with mastectomy or in conservative form

Desde 1980 hasta 1989 fueron tratadas 834 pacientes con cáncer de mama estadios I y II. De estas 834, 401 (edad promedio 58 años), fueron tratadas con mastectomía y radioterapia postoperatoria. Las otras 433 fueron manejadas en forma conservadora con tumorectomía, vaciamiento ganglionar y radioterapia. Doscientos sesenta y tres de las 433 pacientes del grupo conservador (edad media 56 años), recibieron sobredosis al lecho tumoral con Co 60 y 170 pacientes (edad media 50 años), con implante intersticial de Ir 192. Treinta y tres de 834 pacientes recidivaron y las recidivas fueron clasificadas en locales (21), locorregionales (5), inflamatorias (6) y ganglionares (1). Las recidivas se analizaron en función de la edad de las pacientes: menores (82), e iguales o mayores de 40 años (752); del tamaño tumoral: T1 (373) y T2 (457); y del estado ganglionar: NO (493) y N1 (338). Se relacionó la frecuencia de las recidivas con el tipo de tratamiento, el tiempo medio de seguimiento y la interacción entre el tipo de tratamiento y el tamaño tumoral. Se observaron más recidivas en las pacientes menores de 40 años (P=0,005). En la presentación de recidivas no hubo diferencias estadísticamente significativas cuando se las relacionó al tamaño tumoral y al estado de los ganglios al inicio del tratamiento. El tiempo de seguimiento fue un factor importante en la observación de las recidivas. El tipo de tratamiento solamente tuvo relevancia cuando se lo analizó conjuntamente o interactuando con el tamaño tumoral, por lo que en el tratamiento conservador y tumores mayores a 2 cm aparecen más recidivas en el grupo de pacientes mastectomizadas con igual tamaño tumoral, pero esta diferencia no fue estadísticamente significativa. El R.R. (Riesgo Relativo) de recidiva en esta serie es de 1,29 por año de seguimiento. El R.R. de presentación de recidivas en mujeres menores de 40 años fue de 3,12; este riesgo más alto de recidivas en este grupo de pacientes más jovenes depende sólo de la edad y no está relacionado al tipo de tratamiento efectuado.

Cáncer de mama estadios I y II: análisis retrospectivo de las recidivas en 834 pacientes tratadas con mastectomía o en forma conservadora / Breast cancer stage I and II: retrospective analysis of the recurrence in 834 patients treated with mastectomy or in conservative form

Desde 1980 hasta 1989 fueron tratadas 834 pacientes con cáncer de mama estadios I y II. De estas 834, 401 (edad promedio 58 años), fueron tratadas con mastectomía y radioterapia postoperatoria. Las otras 433 fueron manejadas en forma conservadora con tumorectomía, vaciamiento ganglionar y radioterapia. Doscientos sesenta y tres de las 433 pacientes del grupo conservador (edad media 56 años), recibieron sobredosis al lecho tumoral con Co 60 y 170 pacientes (edad media 50 años), con implante intersticial de Ir 192. Treinta y tres de 834 pacientes recidivaron y las recidivas fueron clasificadas en locales (21), locorregionales (5), inflamatorias (6) y ganglionares (1). Las recidivas se analizaron en función de la edad de las pacientes: menores (82), e iguales o mayores de 40 años (752); del tamaño tumoral: T1 (373) y T2 (457); y del estado ganglionar: NO (493) y N1 (338). Se relacionó la frecuencia de las recidivas con el tipo de tratamiento, el tiempo medio de seguimiento y la interacción entre el tipo de tratamiento y el tamaño tumoral. Se observaron más recidivas en las pacientes menores de 40 años (P=0,005). En la presentación de recidivas no hubo diferencias estadísticamente significativas cuando se las relacionó al tamaño tumoral y al estado de los ganglios al inicio del tratamiento. El tiempo de seguimiento fue un factor importante en la observación de las recidivas. El tipo de tratamiento solamente tuvo relevancia cuando se lo analizó conjuntamente o interactuando con el tamaño tumoral, por lo que en el tratamiento conservador y tumores mayores a 2 cm aparecen más recidivas en el grupo de pacientes mastectomizadas con igual tamaño tumoral, pero esta diferencia no fue estadísticamente significativa. El R.R. (Riesgo Relativo) de recidiva en esta serie es de 1,29 por año de seguimiento. El R.R. de presentación de recidivas en mujeres menores de 40 años fue de 3,12; este riesgo más alto de recidivas en este grupo de pacientes más jovenes depende sólo de la edad y no está relacionado al tipo de tratamiento efectuado. (AU)