Rare bowel emphysema with superior mesenteric artery syndrome after surgery.

Superior mesenteric artery syndrome, a rare cause of duodenal obstruction, occasionally requires surgery. Bowel emphysema might also require surgery and might be an ominous sign of a serious condition. We report the case of a 69-year-old Japanese man with left pneumothorax who was also diagnosed as having bowel emphysema and superior mesenteric artery syndrome simultaneously without serious infection after surgery for the pneumothorax. Following gastric decompression via a nasogastric tube, his general condition resolved quickly with no need for surgical intervention. Prompt and precise diagnosis by computed tomography and both adequate judgment and treatment can avoid surgery in such cases.

Anticancer activity of polyoxomolybdate.

Anticancer polyoxomolybdates have been investigated for medical application of polyoxometalates as discrete cluster anions of metal oxides. [NH3Pri]6[Mo7O24].3H2O (PM-8) has been recognized as one of significant antitumoral polyoxomolybdates. PM-8 had shown the growth suppression against several tumors, for examples, Co-4, human colon cancer, MX-1, human breast cancer, and OAT, human lung cancer. PM-8 showed the tumor growth suppression for MKN-45 human gastric cancer in tumor bearing mice. PM-8 inhibited the cell growth of AsPC-1 which depended on the dose with showing DNA ladder formation and DNA fragmentation, and positive Hoechst staining indicating apoptosis. The ratio of apoptotic cells on flow cytometry analysis were 35%, and 57% with treatment of PM-8 after 48, and 72 h, respectively. One of the anti-tumor activity of PM-8 result from the activation of apoptotic pathway. It is thought that polyoxomolybdates will be applied as a novel anti-tumor agent especially against cancers which are difficult to be treated clinically.

Antitumor activity of polyoxomolybdate, [NH3Pri]6[Mo7O24].3H2O, against, human gastric cancer model.

Polyoxometalates are negatively charged inorganic compounds which contain metal ions such as tungsten, molybdenum, vanadium etc. and which make clusters with the surrounding oxygen atoms. [NH3Pri]6[Mo7O24].3H2O (PM-8) was found to be a significant antitumor polyoxomolybdates. It had already been reported that the PM-8 suppressed the growth of Co-4 human colon cancer, MX-1 human breast cancer and OAT human lung cancer xenografted in nude mice. However, the mechanism of the antitumor activity has not been clarified. In this study, the antitumor activity of one of the metal oxide clusters (polyoxometalates), hexabis(isopropylammonium) heptamolybdate trihydrate, [NH3Pri]6[Mo7O24].3H2O (PM-8) were shown in an MTS assay. DNA ladder formation and detection of apoptotic bodies in nuclei were revealed that antitumor activity of PM-8 in MKN45 cells was due to apoptosis. It is concluded that the observation of significant tumor growth suppression of PM-8 in MKN45-bearing mice results from the induction of apoptosis. PM-8 shows promise as a novel anti-cancer agent.

Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.

A novel anti-tumor agent, polyoxomolybdate induces apoptotic cell death in AsPC-1 human pancreatic cancer cells.

Anti-tumoral polyoxomolybdates have been investigated in the course of study of the medical application of polyoxometalates as discrete cluster anions of metal oxides. [NH(3)Pr(i)](6)[Mo(7)O(24)].3H(2)O (PM-8) has been recognized as one of significantly anti-tumoral polyoxomolybdates. PM-8 inhibited the cell growth of human pancreatic cells (AsPC-1) depending on the dose. DNA ladder formation and DNA fragmentation were observed by Hoechst and TUNEL staining and flowcytometry analysis. The ratio of apoptotic cells were 29%, 35%, and 57% with treatment of PM-8 after 24, 48, and 72 h, respectively, which suggested that the anti-tumor activity of PM-8 results from the activation of the apoptotic pathway. Polyoxomolybdates provide promising, novel anti-tumor agent, especially for the treatment of cancers that are difficult to treat.

An attempt to integrate Western and Chinese medicine: rationale for applying Chinese medicine as chronotherapy against cancer.

Current Western medical treatment lays its main emphasis on evidence-based medicine (EBM) and cure is assessed by quantifying the effects of treatment statistically. In contrast, in Chinese medicine, cure is generally assessed by evaluating the patient's "pattern" (Zheng) [cf. Glossary] and medicines are prescribed according to this. We believe that traditional Chinese medicine (TCM) cannot be evaluated precisely according to Western principles, in which a constant amount of the same medicine is given to a group of patients to be evaluated. When assessing cure using TCM, Zheng is more important than the determination of medical effects. This means that quantitative evaluation of TCM treatment can be very difficult. In this paper, we focused on the Yin-Yang [cf. Glossary]balance to determine Zheng, and at the same time attempted to determine the treatment effects by applying the concept of regulation of Yin-Yang according to chronotherapeutic principles. According to Zheng, advanced cancer patients generally lack both Yin and Yang. Chinese medical treatment therefore seeks to supplement both Yin and Yang. However, we divided patients into two groups and compared them with respect to survival. One group was administered a predominantly Yang (Qi) [cf. Glossary] tonic herbal treatment during the daytime, while the other group was administered Yin (Blood) [cf. Glossary] tonics during night time. A comparison of the results of treatment showed that the patients in the group receiving Yang (Qi) replenishment during the daytime lived longer than patients receiving Yin (Blood) nourishment during the night. Moreover, the patients in the daytime Yang (Qi) replenishment group also fared significantly better than patients treated solely by Western methods.

A targeting model of boron neutron-capture therapy to hepatoma cells in vivo with a boronated anti-(alpha-fetoprotein) monoclonal antibody.

We described previously that 10B atoms delivered by monoclonal antibody (mAb) exerted a cytotoxic effect on AH66 cells in a dose-dependent manner upon thermal neutron irradiation in vitro. In the present study, the delivering capacity of boronated anti-(alpha-fetoprotein) (AFP) mAb to carry 10B atoms to AFP-producing tumor xenografts in nude mice was determined. Boronated mAb was prepared by conjugating 50 mM 10B compound to an anti-AFP mAb (2 mg/ml) using N-succinimidyl-3-) (2-pyridyldithio) propionate. The number of 10B atoms conjugated directly to the mAb was estimated to be 459/antibody by prompt gamma-ray spectrometry. Boron concentrations in tumor tissue obtained 12, 24, 72, and 120 h after injection of 3.0 mg 10B-conjugated anti-AFP mAb were 11.10 +/- 3.12 (SD, n = 6). 29.30 +/- 5.11, 33.02 +/- 11.8, and 12.91 +/- 5.62 ppm respectively. For control 10B-conjugated anti-dinitrophenol (DNP) mAb, the values were 9.59 +/- 0.99, 10.37 +/- 2.86, 10.00 +/- 2.95, and 8.83 +/- 4.71 ppm respectively. The concentrations in blood were less than 0.40 +/- 0.10 ppm with anti-AFP mAb and less than 0.51 +/- 0.15 ppm with anti-DNP mAb at each sampling time (12, 24, 72, and 120 h). The number of 10B atoms delivered to the tumor cells was calculated to be 0.62 x 10(9), 1.63 x 10(9), 1.84 x 10(9) and 0.72 x 10(9) at each sampling time after injection of 10B-anti-AFP mAb. The amount of 10B atoms necessary for effective boron neutron-capture therapy was estimated to be 10(9)/tumor cell. We were able to carry 1.84 x 10(9) 10B atoms to AH66 tumor cells by using 10B-anti-AFP mAb. The accumulation reached its peak 72 h after injection. These data indicated that the 10B-conjugated antitumor mAb could deliver a sufficient amount of 10B atoms to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal neutron irradiation.

Design of fusogenic liposomes using a poly(ethylene glycol) derivative having amino groups.

As a novel fusogenic liposome, we designed liposomes modified with poly(glycidol) having beta-alanine residues, which is a poly(ethylene glycol) derivative with positively charged groups. The polymer-modified liposomes of egg yolk phosphatidylcholine (EYPC) and dioleoylphosphatidylethanolamine (DOPE) were prepared by reverse phase evaporation. Fusion of the polymer-modified liposomes with anionic liposomes consisting of phosphatidic acid and DOPE was investigated. Fusion ability of the polymer-modified liposomes increased with increasing amount of the polymer fixed on the liposome. Also, inclusion of DOPE was necessary for the generation of the fusion ability of the polymer-modified liposomes. CV1 cells treated with the polymer-modified DOPE/EYPC liposomes containing calcein displayed diffuse fluorescence, suggesting that calcein was introduced into the cytoplasm. In contrast, only punctual fluorescence was observed in the cells treated with the polymer-modified EYPC liposomes containing calcein, indicating that calcein remained in the endosome and/or lysosome. In addition, COS1 cells were transfected efficiently by treatment with the polymer-modified EYPC/DOPE liposomes containing pSV2cat plasmid, whereas the transfection was not induced by treatment with the polymer-modified EYPC liposomes. Close correlation between fusion ability of the polymer-modified liposomes and their ability to deliver their contents to the cytoplasm implies that membrane fusion plays an important role in the liposome-mediated cytoplasmic delivery.

Does the timing of surgery for breast cancer in relation to the menstrual cycle or geomagnetic activity affect prognoses of premenopausal patients?

We examined the records in 36 breast cancer patients treated between 1990 and 2001, and compared them for relapse-free survival with reference to the phases of menstrual cycle defined by Hrushesky et al. and Senie et al. During the follow-up period, seven patients suffered a relapse and one died of another disease without relapsed breast cancer. The recurrence rate and relapse-free survival were not significantly different with the menstrual timing of surgery. However, patients with early breast cancer operated during the follicular phase and those with advanced breast cancer resected during the luteal phase appeared to show better prognosis than corresponding controls operated during the other phases. On the other hand, the correlation between geomagnetic activity and prognosis of breast cancer was also investigated. High geomagnetic activity during operation significantly affected the prognosis of the disease in an adverse fashion. This adverse influence was more marked in the patients operated during the luteal period. Since the menstrual cycle has no clear relation to the prognosis of breast cancer, the geomagnetic activity might affect them via other pathways than the menstrual cycle.

Correlation between timing of surgery in relation to the menstrual cycle and prognosis of premenopausal breast cancer patients.

The timing of surgery in relation to menstrual phase might affect the progress of disease in premenopausal women with operable breast cancer. In the present study, the records were examined of 28 such cases treated between 1990 and 1999, and compared for recurrence-free survival with reference to the phases of the menstrual cycle defined by Hrushesky and Senie. During the follow-up period, breast cancer relapse occurred in five patients, and one patient died of another disease unconnected with recurrent breast cancer. The recurrence rate was not significantly different between two phases classified by either Hrushesky or Senie. However, patients with early-stage breast cancer operated during the perimenstrual phase and those with advanced breast cancer which was resected during the peri-ovulatory phase appeared to have a better prognosis than patients operated on during the other phases. Since the prognosis for breast cancer patients is dependent not only on the menstrual cycle but also on many other factors, it is concluded that the menstrual cycle cannot constitute an absolute prognostic factor.

Chronotherapy for cancer.

Cancer chronotherapy is attracting attention as a novel and logical therapy in which anti-cancer drugs are administered with optimal timing according to circadian rhythms of anti-cancer action and those of adverse effects on normal cells. Advances in chronobiology have identified the suprachiasmatic nucleus (SCN) as the center of biological rhythms and the area in which clock genes such as PER1, PER2, PER3, CLOCK, BMAL1, TIM, CRY1, CRY2, tau act to generate and coordinate biological rhythms. These findings have led to the development of chronotherapy. Clinically, patients with advanced gastrointestinal cancer have been treated by chronomodulated chemotherapy with good response. For colorectal cancer patients with unresectable liver metastases, chronotherapy with l-OHP + 5-FU + FA (folinic acid) has been reported to allow complete surgical resection of liver metastases, resulting in 39-50% 5-year survival. Many believe that chronotherapy will become accepted as a refined and advantageous therapeutic option for not only cancer but also for other diseases, due to its universally applicable principles.

A molecular biological study of anti-tumor mechanisms of an anti-cancer agent Oxaliplatin against established human gastric cancer cell lines.

We report that preoperative administration of Oxaliplatin, a new anti-cancer platinum agent, is an effective treatment for gastric cancer. The purpose of this in vitro study is to determine whether Oxaliplatin induces apoptosis in established human gastric cancer cell lines. Five established gastric cancer cell lines are used: MNK45, KATO-III, OKAJIMA, MNK28 and MNK74. Chemosensitivity to l-OHP is studied using a growth inhibition test. Induction of apoptosis in gastric cancer cells is analyzed by assessing DNA ladder formation, DNA fragmentation and actin cleavage. While all five gastric cancer cell lines are sensitive to Oxaliplatin, the poorly differentiated lines are the most sensitive. DNA ladder formation and/or DNA fragmentation are detected in all gastric cancer cell lines. However, actin cleavage is not detected in any of the cell lines. Oxaliplatin has an anti-cancer effect on human gastric cancer cell lines, particularly cell lines of poorly differentiated adenocarcinoma, indicating that Oxaliplatin would be an effective treatment for poorly differentiated gastric cancer. Oxaliplatin induces apoptosis in gastric cancer cell lines, but actin cleavage is not detected in cancer cells. This finding suggests that (1) the apoptotic caspase pathway leads mainly to DNA condensation and fragmentation, and (2) caspase-independent apoptotic pathways may be activated when gastric cancer cells are treated with Oxaliplatin.

Surgery in patients with HIV infection: indications and outcome.

We reviewed the records of 12 patients with HIV infection (one stage I, three stage II, two stage III, six stage IV) who received 15 surgical procedures under general or lumbar/epidural anesthesia. We discussed surgical indications, their poor wound healing and precautions for preventing the risk of transmission of HIV to health care workers. Six emergency and nine elective operations were performed. Postoperative complications developed after three emergency and three elective operations. Ten patients showed delay of wound healing which was not directly correlated with the CD4+ cell count. No operative deaths occurred. In any stage of HIV infection, not only palliative but also curative operations can be performed as long as HIV infection, opportunistic infections and HIV-related neoplasms can be controlled. Late stage wound healing is poor, but the wound will heal without keloid formation, although it takes two to three times longer than usual. For operating on patients with HIV infection precautions for preventing needle sticks, sharp injuries and blood exposure should be learned and used by health care workers. As a result, surgical staff members will be able to perform operations safely on HIV-infected patients to improve both quality of life and the prognosis of their disease.

Pilot study for preoperative administration of l-OHP to patients with advanced scirrhous type gastric cancer.

A new DACH platinum complex, l-OHP, was developed by Kidani as an anticancer agent. A clinical trial took place in Europe which demonstrated its therapeutic efficacy for colorectal cancer. An effective treatment, especially chemotherapy for patients with a advanced scirrhous type gastric cancer, has not yet been established. An in vitro study showed that l-HOP inhibited cell growth in human gastric cancer cell lines. Our pilot study determined the efficacy of preoperative administration of l-OHP, 67 mg/m2 to 100 mg/m2, every 2-3 weeks, for two to three cycles, in five patients with this disease (Stage III and IV) roentogenoscopically and histologically. The platinum concentration in the tissues was also measured. By X-ray examination of the stomach at the time of pre- and post-administration of l-OHP, extension of the lesional gastric wall was observed. Histologically three Grade 2 responses and two Grade 1a responses were obtained according to the criteria presented by Japanese Research Society for Gastric Cancer. The mean platinum concentrations in the lesional tissues were 0.98 ppm and 0.5 ppm in the patients administered l-OHP for three and two cycles respectively. There was no toxicity that prevented surgery. These preliminary results showed the possibility that 1-OHP would be effective for patients with advanced scirrhous type gastric cancer as a neoadjuvant therapy.

Diagnosis of peripapillary carcinoma: endoscopic findings.

During the period 1982-1988, 8 patients were admitted with peripapillary carcinoma. Pancreatico-duodenectomy (PD) was successfully carried out on 7 occasions but only 3 patients are alive today. Early diagnosis of this disease is therefore mandatory. Endoscopic sphincterotomy is particularly useful for the diagnosis of the non-exposed type of carcinoma in the peripapillary region.

Bcl-2, Bcl-xL and c-FLIP(L) potentially regulate the susceptibility of human peripheral blood monocyte-derived dendritic cells to cell death at different developmental stages.

We examined the susceptibility of human monocyte-derived dendritic cells (DCs) to spontaneous and CD95-mediated cell death at different developmental stages. Time course experiments revealed that the susceptibility of mature dendritic cells (mDCs) to spontaneous cell death was significantly lower than that of immature dendritic cells (iDCs) in a long-term culture under cytokine-free conditions, and the treatment with GM-CSF rescued these cells from spontaneous cell death at the late culture period. iDCs and mDCs expressed similar levels of CD95 whereas both cell types were relatively resistant to CD95-mediated cell death. Antigen (Ag)-specific and nonspecific cognate interaction with T cells failed to cause cell death of iDCs and mDCs. iDCs constitutively expressed transcripts and intracellular products of Bcl-2 and Bcl-xL, but not cellular FLICE-inhibitory protein(long (c-FLIP(L)), while the increased expressions of Bcl-2, Bcl-xL and c-FLIP(L) were observed in mDCs. These results suggest that the selective expressions of Bcl-2, Bcl-xL and c-FLIP(L) may be involved in the difference in the susceptibility to cell death between iDCs and mDCs.

Inhibition of growth of human breast cancer cells in culture by neutron capture using liposomes containing 10B.

Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4 microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation.

[Boron neutron capture therapy using 10B entrapped anti-CEA immunoliposome].

A new murine monoclonal antibody (2C-8) was prepared by immunizing mice ip with CEA producing human pancreatic cancer cell line, AsPC-1.SDS-PAGE and Western blot analysis showed that 2C-8 monoclonal antibody recognized CEA and NCA. This anti-CEA monoclonal antibody was conjugated with large multilamellar liposomes incorporated 10B compound (Cs2 10B12H11SH). This immunoliposomes applicated to boron neutron capture therapy. AsPC-1 cells were incubated with the 10B-Lip-MoAb(CEA) for 8 hours. After the irradiation with thermal neutron (1 x 10(11)-1 x 10(13) n/cm2), boronated AsPC-1 cells were showed decreasing uptake of 3H-TdR compared with control group. The numbers of 10B atoms in liposomes bound to an antibody were in proportion to the dose of 10B compounds added and maximum number of 10B atoms was approximatory 1.2 x 10(4)/Ab. These data indicated that the immunoliposomes could deliver highly amount of 10B atoms to the tumor cells and exert cytotoxic effect by thermal neutron. BNCT with immunoliposome may be useful to the non resectable malignant tumors in clinical application.

Neutron capture autoradiographic study of the biodistribution of 10B in tumor-bearing mice.

For the study on boron neutron capture therapy, the whole-body sections of tumor-bearing mice infused with 10B attached to CR-39 plastic track detectors were exposed to thermal and cold neutron beams. Neutron capture autoradiographic images obtained by the cold neutron irradiation were extremely superior in quality to those of the thermal neutron beams. From the autoradiographic images, the 10B reaction dose of the neutron-induced particles was estimated using the differential LET distribution.

Microscopic response of radiation on imaging plates.

The microscopic response of alpha particles on an imaging plate was studied experimentally. It is proved that a single alpha event can be discriminated from background signals and be recorded on the imaging plate. The spatial resolution of the dose distribution was found to be 43 +/- 2 microns when alpha particles were injected perpendicularly. The observed output signals are well described by the deposited energy.