Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: Report of a case

A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46–47°C perfusate containing 40 g/ml of mitomycin C (MMC) and 200 g/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m² and 21 mg/m² of MMC, and ten doses of 710 mg/m² of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m² of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery.     

Radioimmunodetection of cancer of gastrointestinal tract and liver metastasis with I-131 anti-CEA and I-131 anti-CA19-9 monoclonal antibody cocktail (IMACIS-1)

We evaluated the intravenous infusion of a cocktail of I-131 anti-CEA and anti-C A19-9 monoclonal antibody F(ab’)2 (IMACIS-1) in patients with gastrointestinal neoplasm and liver metastases in order to assess its efficacy in detecting the presence of cancer. Seven patients with primary or recurrent gastrointestinal cancer in whom liver metastases were also detected were studied. Accumulation of radioactivity in the primary tumor was seen in only one patient. Visualization of the liver metastases was achieved in all patients. Thus detection of liver metastasis was better than in primary or recurrent tumors. While tumor visualization was most often seen in the 3 day image, optimal visualization of the tumor was seen at 5–7 days. There was no correlation between the serum concentration of CEA or CA19-9 and the visualization of tumors. Serum kinetics of I-131IMACIS-1 showed biexponential components with a 1st phase T_1/2 of 5.0 hours and 2nd phase T_1/2 of 34.7 hours. The mean whole body (I-131) half-life determined from the whole-body scans was 1.95 days. The mean urinary excretion of I-131 in 7 days was 85%. This value agreed closely with total radioactivity retention detected by scanning. This series of studies demonstrated the potential utility of a cocktail of antibodies consisting of an anti-CEA and an anti-CA19-9 monoclonal F(ab’)₂.     

Substitution at the F-ring N-imide of the indolocarbazole antitumor drug NB-506 increases the cytotoxicity, DNA binding, and topoisomerase I inhibition activities.

The antitumor drug NB-506, which is currently undergoing phase I/II clinical trials, contains a DNA-intercalating indolocarbazole chromophore substituted with a glucose residue. In addition to interacting with DNA, the drug stabilizes the topoisomerase I-DNA covalent complex. To reinforce the DNA binding and anti-topoisomerase I activities of NB-506, an analogue containing a new substituent on the naphthalimide ring F was synthesized. The N-formylamino group of NB-506 has been replaced with a more hydrophilic group, N-bis(hydroxymethyl)methylamino. In this study we show that the incorporation of a longer substituent on the N6 position effectively reinforces both the interaction with DNA and the capacity of the drug to maintain the integrity of the topoisomerase I-DNA covalent complexes. The strength and the mode of binding of the drugs to DNA were studied by complementary biophysical techniques including absorption, fluorescence, and circular and linear dichroism. Various biochemical procedures were applied to investigate the effects on human topoisomerase I using plasmid DNA as well as restriction fragments. The drug binding sites and the positions of the topoisomerase I-mediated cleavage sites were mapped with nucleotide resolution using footprinting and sequencing techniques. Cytotoxicity measurements performed with various human cancer cell lines (HCT-116, DLD-1, MKN-45) indicate that the newly designed drug is 3 to 4 times more toxic to colon and gastric cancer cells than NB-506. Therefore, the results suggest that the antitumor activity of indolocarbazole-based drugs can be enhanced by incorporating DNA and/or topoisomerase I reactive groups. They also support the hypothesis that the substituent on the imide nitrogen on the F ring of NB-506 has direct interaction with the molecular target. The study helps to define the structure-activity relationships in the indolocarbazole series of antitumor agents targeting topoisomerase I.     

Anti-pressor effect of a Chinese-Japanese herbal medicine, saiko-ka-ryukotsu-borei-to on hemodynamics in rabbits

Saiko-ka-ryukotsu-borei-to (TJ-12) is a traditional Chinese-Japanese medicinal mixture clinically used for the treatment of hypertension and/or atherosclerosis concurrent with neurotic disorders. Study on the effect of TJ-12 on the vasoconstriction of cutaneous arterioles induced by nor-adrenaline (NA) was carried out using a rabbit ear chamber (REC) under conscious conditions. Before and after oral administration of TJ-12 everyday for 2 weeks, the same position of an arteriole within a REC was analyzed using an image shearing monitor every minute up to 15 min after varying doses (0.3, 1.0, 3.0 and 10.0 micrograms/kg i.v.) of NA. The changes of mean arteriolar diameter and vasomotion amplitude, before and after feeding of TJ-12 (1% w/w) supplemented diet were compared in the same position. Consequently, the pretreatment with TJ-12 significantly attenuated the changes of mean diameter of NA-induced vasoconstriction and also shortened its duration. In addition, concurrent with its cutaneous microcirculatory response, the pretreatment with TJ-12 systemically suppressed the increase of blood pressure under NA-induced vasoconstriction. These results suggest that the anti-pressor effect of TJ-12 might be apparently attributable to the inhibition of NA-induced vasoconstriction.     

Brain lesion in congenital myotonic dystrophy

Congenital myotonic dystrophy (CMyD) affects the brain, causing mental changes and psychomotor retardation. However, the pathophysiology of the brain dysfunctions in CMyD remain to be clarified. We described two cases of CMyD with brain abnormalities. Case 1 was diagnosed as having ventricular dilation at 17 days after birth, and died at 3 years and 6 months. Case 2 was diagnosed as having ventricular dilation at birth, and died at 1 year and 3 months. Pathologically, both cases showed remote hypoxic ischemic brain damage and leptomeningeal glioneuronal heterotopia (LGH). In our patients, the white matter changes may have been caused by perinatal asphyxia, and LGH by embryological abnormalities. Taken our data and those of previous reports together, it is suggested that cerebral abnormalities in CMyD are ascribed to both hypoxic ischemic changes and histogenetic abnormalities.     

Histological findings after angioplasty using conventional balloon, radiofrequency thermal balloon, and stent for experimental aortic coarctation

Abstract Background : Use of balloon angioplasty or stent implantation has been reported to be effective in relieving coarctation of the aorta. However, restenosis frequently occurs after balloon angioplasty for native aortic coarctation in small infants, and sometimes develops after stent implantation because of vessel growth. The causes of restenosis remain uncertain. The purpose of this study was to assess the histologic differences in vascular responses to angioplasty using conventional balloon, radiofrequency thermal balloon (RFTB), or stent for experimental aortic coarctation. Methods : The authors surgically created an aortic coarctation model using 14 puppies. Angioplasty using conventional balloon, RFTB, or stent was performed 1 month after the initial operation. At the acute or chronic phase after angioplasty, the animals were killed and histologic studies were performed. Results : More vascular injuries were noted in the specimens from animals undergoing conventional angioplasty than in those with RFTB or stent. However, neointimal hyperplasia was seen more often after RFTB or stent because of the proliferation of smooth muscle cells from the tunica media, caused by secretion of growth factors. Apoptosis reached a peak 1?2 weeks after angioplasty, regardless of the type of intervention. Conclusions : The authors conclude that angioplasty with RFTB or stent can provide relatively small injuries in the vessel wall for aortic coarctation, but care must be taken to prevent restenosis caused by intimal hyperplasia, because neointima hyperplasia is more frequent after RFTB or stent.     

铜绿假单胞菌感应分子对照质粒及整合突变株的构建

目的 研究细胞间信息传递机制之一假单胞菌喹诺酮信号(PQS)在铜绿假单胞菌发病机制中的作用.方法 基于基因融合分析在转录研究中的实用性,构建了两种PQS相关对照质粒和整合突变株.一种是酶切质粒pYHP441获得pqsA'-lacZ片段后,亚克隆入质粒miniCTX-1中,构建成pqsA'的阳性表达质粒,随后将构建的质粒,通过双亲交配过程整合入野生型铜绿假单胞菌株PAO-1染色体组中;另一种是通过点特异插入诱变策略,将四环素基因盒插入启动子pqsD和pqsE之间,构建的阴性质粒转化入大肠杆菌S17-1株后,和上述pqsA'阳性表达突变株进行双亲交配过程.结果 针对今后PQS的相关研究,构建得到稳定表达PQS的质粒和阳性突变株作为阳性对照.构建获得pqsA-E启动子敲除质粒和相应PQS表达受阻的整合突变株作为阴性对照.结论 两种质粒和整合突变株的构建成功,使得PQS的相关研究结论具有客观性、精确性和有效性.