P53 and rb alterations in operable breast-cancer

We analyzed association between p53 and/or Rb expression and clinicopathologic variables or Ag-NOR counts, and then ascertained whether p53 and/or Rb expression would be useful for estimating prognosis in 81 breast cancer patients. Positive p53 expression was significantly associated with post-menopausal status, axillary lymph node metastases and Ag-NOR counts, whereas low level Rb expression was significantly associated with tumor size. Moreover, the combination of p53 and Rb expression was significantly associated with Ag-NOR counts, although there was no significant association between p53 and Rb expression. In the univariate study, p53 expression as well as age and axillary lymph node metastases were significantly associated with survival, whereas Rb expression was not. In the multivariate study, p53 and/or Rb expression did not provide independent prognostic information, although axillary lymph node metastases was an important factor affecting survival. Our findings suggest that p53 and/or Rb expression may reflect tumor proliferation of breast cancer, but the prognostic value of such assays is limited.     

A case with breast cancer under the nipple who underwent breast conserving treatment

Although breast conserving treatment (BCT) has become the standard therapy for early breast cancer, breast removal is still recommended for patients with a tumor beneath the nipple or with Paget’s disease. We have employed transposition of a latissimus dorsi myocutaneous (LD-MC) flap after wide local excision of a tumor with the nipple-areola complex. A new nipple-areola complex was reconstructed on the LD-MC flap after breast irradiation. Utilizing reconstructive techniques, BCT will likely become the treatment of choice for more patients with early breast cancer.     

Selective localization of gelatinase A,an enzyme degrading β-amyloid protein,in white matter microglia and in Schwann cells

Gelatinase A is an enzyme capable of cleaving soluble -amyloid protein (AP), and may function as an -secretase to produce secretory forms of amyloid precursor protein. We examined gelatinase A immunoreactivity in the brains and posterior roots of neurologically normal, lacunar stroke, Alzheimer disease (AD), amyotrophic lateral sclerosis, progressive supranuclear palsy and myasthenia gravis cases. The gelatinase A antibody stained only microglial cells in the white matter in all the brain tissues. In AD brain, the reactive microglia located in the center of classical senile plaques, as well as in other microglial cells in the gray matter, showed no immunoreactivity. Gelatinase A in white matter microglial cells may play a role in preventing local deposition of AP. In the posterior root, Schwann cells had positive immunoreactivity. As with other metalloproteases, gelatinase A in Schwann cells may play an antiproliferative role.     

The renal lesions that develop in neonatal mice during angiotensin inhibition mimic obstructive nephropathy

BACKGROUND: Inhibition of angiotensin action, pharmacologically or genetically, during the neonatal period leads to renal anomalies involving hypoplastic papilla and dilated calyx. Recently, we documented that angiotensinogen (Agt -/-) or angiotensin type 1 receptor nullizygotes (Agtr1 -/-) do not develop renal pelvis nor ureteral peristaltic movement, both of which are essential for isolating the kidney from the high downstream ureteral pressure. We therefore examined whether these renal anomalies could be characterized as "obstructive" nephropathy. METHODS: Agtr1 -/- neonatal mice were compared with wild-type neonates, the latter subjected to surgical complete unilateral ureteral ligation (UUO), by analyzing morphometrical, immunohistochemical, and molecular indices. Agtr1 -/- mice were also subjected to a complete UUO and were compared with wild-type UUO mice by quantitative analysis. To assess the function of the urinary tract, baseline pelvic and ureteral pressures were measured. RESULTS: The structural anomalies were qualitatively indistinguishable between the Agtr1 -/- without surgical obstruction versus the wild type with complete UUO. Thus, in both kidneys, the calyx was enlarged, whereas the papilla was atrophic; tubulointerstitial cells underwent proliferation and also apoptosis. Both were also characterized by interstitial macrophage infiltration and fibrosis, and within the local lesion, transforming growth factor-beta 1, platelet-derived growth factor-A and insulin-like growth factor-1 were up-regulated, whereas epidermal growth factor was down-regulated. Moreover, quantitative differences that exist between mutant kidneys without surgical obstruction and wild-type kidneys with surgical UUO were abolished when both underwent the same complete surgical UUO. The hydraulic baseline pressure was always lower in the pelvis than that in the ureter in the wild type, whereas this pressure gradient was reversed in the mutant. CONCLUSION: The abnormal kidney structure that develops in neonates during angiotensin inhibition is attributed largely to "functional obstruction" of the urinary tract caused by the defective development of peristaltic machinery.     

Cytoreductive surgery and sandwich therapy with chemohyperthermic peritoneal perfusion and intra-aortic chemotherapy for peritoneal dissemination in gastric cancer

Cytoreductive resection (RST), chemohyperthermic peritoneal perfusion (CHPP) and/or intra-aortic chemotherapy (IA-chemo) were performed for peritoneal dissemination in gastric cancer. Ninety-six patients with peritoneal dissemination were grouped into tubercular (TB), 40; nodular (ND), 31; diffuse (DF) type, 19; and others, 6, respectively, by the gross findings. Sixty-three patients underwent RST. Fifty-nine patients received CHPP by 10-liter heated saline. Thirty patients underwent intra-aortic catheterization for the IA-chemo. The 1-year and 2-year survival rate (1-ysr and 2-ysr) of the RST(+) group were 47% and 10% significantly greater than the 9% and 0% of the RST(-) group (p<0.001). The 1-ysr and 2-ysr of the CHPP(+) group were 37% and 11% significantly greater than the 27% and 0% of the CHPP(-) group (p=0.04). In the TB type the 1-ysr and 2-ysr of the former was 43% and 8% significantly greater than the 15% and 0% of the latter (p=0.04). But there was no significant difference in survival time between the CHPP(+) and the CHPP(-) group in the ND type (p=0.22) or in the DF type (p=0.42). The 1-ysr and 2-ysr of the IA-chemo(+) group were 49% and 19% significantly greater than the 27% and 2% of the IA-chemo(-) group (p<0.01). In the DF type the 1-ysr and 2-ysr of the former was 50% and 33% significantly greater than the 8% and 0% of the latter (p=0.02). However, there was no significant difference in survival time between the IA-chemo(+) and the IA-chemo(-) group in the TB type (p=0.06) or in the ND type (p=0.50). Moreover, the effect of the combination therapy of CHPP and IA-chemo (the sandwich therapy, SDW) were examined. The 1-ysr and 2-ysr of the SDW(+) group were 49% and 22% significantly greater than the 24% and 0% of the SDW(-) group (p=0.002). The sandwich therapy should be performed in addition to cytoreductive surgery for improvement of prognosis in the patient with intractable peritoneal dissemination.     

Controlled trial of thyrotropin releasing hormone tartrate in ataxia of spinocerebellar degenerations

The clinical efficacy, dose-response relationship, and safety of TRH-T (thyrotropin releasing hormone tartrate) were assessed in 290 patients with spinocerebellar degeneration (SCD) in a 2-week, double-blind study using placebo as control. 254 patients satisfied the criteria for inclusion in evaluation of the drug efficacy. The patients were treated with TRH-T in an intramuscular dose of 2 mg, 0.5 mg or 0 mg (placebo) as TRH once a day for 2 weeks. Clinical responses to these treatments were evaluated 3 times: at the end of weeks 1 and 2 of treatment and a week after the end of treatment. The results of "global improvement rating" as well as those of "ataxia improvement rating" showed that both 2 mg and 0.5 mg TRH-T treatments were significantly superior to placebo treatment in patients with predominantly cerebellar form of SCD. The effect was well maintained a week after the end of the 2-week treatment in the patients who were given TRH-T in daily dose of 2 mg and showed improvement at the end of treatment. The results of "improvement rating of each symptom" revealed that 2 mg treatment was significantly more effective than placebo for disorders of standing, gait, speech and writing. In the patients who had no pyramidal involvement or disorder of deep sensation, the drug efficacy and dose-response relationship were evident. Adverse reactions to the drug such as headache, feeling febrile and nausea were observed in 50% of the patients on 2 mg treatment, in 38% of those on 0.5 mg treatment and in 21% of those on placebo patient, however, discontinued treatment because of adverse reactions.     

Proliferative activity in advanced gastric-cancer with ki-67 and propidium iodide - analysis by flow-cytometry

By setting the cut-off line at the level as used in a negative control study without primary antibody in the same sample, the Ki-67 labeling rate was calculated by the Ki67-DNA dual fluorescence analysis. The mean Ki-67 labeling rate of 28 advanced gastric cancer was 45.1% (13.9-76.3%). The Ki-67 labeling rates were significantly higher for larger size tumor (p<0.05), peritoneal metastasis and advanced stage (p<0.01). This is the first report that cycling cells are calculated by setting the cut-off line for solid tumors. Use of this flow cytometric procedure substantially facilitates the quantification of proliferating cells in gastric cancer.     

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

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Resumen La perfusión hipertérmica continua (PHTC) con agentes anticancerosos (mitocina G y cisplatino) y solutión salina fue realizada en pacientes con cáncer gástrico con diseminación peritoneal después de resección de la lesión primaria, y el efecto de PHTC fue determinado mediante reexploración (operación de second look, OSL). La población de pacientes está constituída por 41 casos de cáncer gástrico con diseminación peritoneal pero sin metástasis hepáticas, tratdos en el curso de los últimos 6 años. La sobrevida media global fue de 437 dias (rango 28 a 1925 días) desde la PHTC hasta la muerte y la tasa de sobrevida a 3 años fue 28.5%. La OSL reveló una notoria disminución de la diseminación peritoneal en 7 (50%) de 14 casos y desaparición de la ascites después de sólo un ciclo de PHTC en 7 de 9 casos con ascitis. Sobrevida de 3 años ocurrió en 4 casos. Los efectos colaterales fueron insuficiencia renal en 2 casos (5%), leucopenia en 2 casos (5%) y perforación del intestino delgado en 1 caso (2%). Los anteriores resultados sugieren que la PHTC es eficaz en el tratamiento del cáncer gástrico con diseminación peritoneal.

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Résumé La perfusion péritonéale continue hyperthermique (PPCH) avec des agents anticancéreux comme le mitomycine C et la cis-platine avec sérum physiologique chauffé a été instaurée lorsqu'une carcinose d'origine gastrique a été trouvée. Les effets de la PCH ont été évalués chez 16 patients lors d'un second-look (SL). Cette étude concerne 41 patients avec carcinose péritonéale sans métastase hépatique observés au cours des 6 dernières années. La survie globale médiane était de 437 jours (extrêmes 28 à 1925 jours): le taux de survie a 3 ans était de 28.5%. Les lésions avaient diminué de façon notable chez 7 (50%) de 14 patients. L'ascite a disparu dans 7 des 9 cas. Une survie à long terme (3 ans) a été notée dans 4 cas. Les effets secondaires ont été une insuffisance rénale dans 2 cas (5%), une leucopénie dans 2 cas (5%) et une perforation de l'intestin grêle dans un cas (2%). Les résultats suggèrent que la PPCH est efficace dans le traitement du cancer gastrique avec dissémination péritonéale.