Search

To establish a novel quantitative method that automatically excludes the red bone marrow and accurately quantifies the tumor volume on whole-body magnetic resonance imaging using updated imaging software. To also evaluate the association between the quantified tumor volume and the prognosis of patients with metastatic prostate cancer.This prospective analysis included patients diagnosed with metastatic hormone-sensitive or metastatic castration-resistant prostate cancer between 2017 and 2022. We developed an imaging software (Attractive BD_Score) that analyzed whole-body diffusion-weighted and in-phase and opposed-phase T1-weighted images to automatically exclude the red bone marrow. The quantified tumor volume was compared with that quantified by traditional whole-body diffusion-weighted imaging without red bone marrow exclusion. Prostate-specific antigen progression-free survival, time-to-pain progression, and overall survival were evaluated to assess the prognostic value of the quantified tumor volume.The quantified tumor volume was significantly smaller than that quantified by the traditional method in metastatic hormone-sensitive (median: 81.0 ml vs. 149.4 ml) and metastatic castration-resistant (median: 29.4 ml vs. 63.5 ml) prostate cancer. A highly quantified tumor volume was associated with prostate-specific antigen progression-free survival (p = 0.030), time-to-pain progression (p = 0.003), and overall survival (p = 0.005) in patients with metastatic hormone-sensitive prostate cancer and with poor prostate-specific antigen progression-free survival (p = 0.001) and time-to-pain progression (p = 0.005) in patients with metastatic castration-resistant prostate cancer.Our imaging method could accurately quantify the tumor volume in patients with metastatic prostate cancer. The quantified tumor volume can be clinically applied as a new prognostic biomarker for metastatic prostate cancer.

Introduction Surgical resection should be considered for giant adrenal cysts if they are functional, if malignancy cannot be ruled out, or if there is a risk of bleeding. However, preventing cyst damage, including fluid leak, and ensuring a good field of view could be challenging in laparoscopic surgery. We report on our successful use of the SAND balloon catheter in laparoscopic adrenalectomy. Case presentation The patient was a 40-year-old man with a right adrenal cyst that exhibited growth tendency. We performed laparoscopic adrenalectomy using a SAND balloon catheter through a preexisting port. Use of the catheter allowed for not only aspiration of the cyst fluid without leakage into the operative field but also gentle grasping of the cyst wall, which enabled us to easily remove the adrenal gland, including the cyst. Conclusion Use of the SAND balloon catheter facilitates safe and easy laparoscopic resection of giant adrenal cysts.

We are developing cross-shaped semi-submersible floating structure composed of simple and lean stiffened plate structure. In this paper, we introduce the features and development studies of our 12MW semi-submersible floating offshore wind turbine. First, we introduce the main features of it. Second, we introduce the tank test of it, the purpose of which is verifying the behavior under the condition only wave load is applied. As a result of tank test, we verified motion response which is calculated by numerical calculation tool based on potential theory is well reasonable. Third, we introduce the initial structural analysis, the purpose of it is to decide initial scantling. Finally, we introduce the coupled analysis of our 12MW semi-submersible floating offshore wind turbine. Concerning the model of coupled analysis, we verified it from the several points of view. We verified the motion response of it under the condition that only wave load is applied. Compared to the result of numerical calculation and tank test, we confirmed motion response of coupled analysis model is valid. We also confirmed the natural frequency of the whole structure and the displacement due to both rigid motion and elastic deformation are reasonable compared to the result of FEM analysis. Then, we performed the coupled analysis under the condition that both wave load and wind load are applied considering the effect of turbine’s operation.

Introduction Prostate sarcoma is an extremely rare disease with a poor prognosis. Undifferentiated pleomorphic sarcoma has never been described in the prostate.Case presentation: A 27-year-old man complained of frequent urination and dysuria for several years. Various examinations were suggestive of prostate sarcoma. The pathological diagnosis was confirmed as prostate sarcoma via ultrasound-guided transrectal needle biopsy. Because the location of the tumor in the prostate was confirmed by magnetic resonance imaging, we performed robot-assisted radical prostatectomy. The final pathological diagnosis was undifferentiated pleomorphic sarcoma. Local recurrence occurred at the front of the rectum 2 months after surgery. Although chemotherapy and radiotherapy were initially effective, he died 18 months after surgery. Conclusion Undifferentiated pleomorphic sarcoma of the prostate is believed to have a poor prognosis. When selecting the surgical procedure, functionality should be considered for individual cases with complete resection.

To assess the impact of patients' interest in sex on the satisfaction after robot-assisted radical prostatectomy, longitudinal changes of urinary and sexual functions and bothers were evaluated.A total of 101 patients underwent robot-assisted radical prostatectomy in our institution. Based on sexual interest, they were divided into the high-interest and low-interest groups. Overall satisfaction, urinary function, urinary bother, sexual function, and sexual bother were evaluated using the expanded prostate cancer index composite questionnaire preoperatively and at 1, 3, 6, and 12 months after robot-assisted radical prostatectomy. We investigated the associations between the overall satisfaction and urinary function/urinary bother/sexual function/sexual bother scores (with higher score indicating better function and less impairment).In the high-interest group (n = 45), satisfaction correlated with high urinary function and urinary bother scores early after robot-assisted radical prostatectomy (urinary function: 1 and 3 months, urinary bother: 3 months postoperatively; P 0.05) and then with high sexual bother score thereafter (sexual bother at 6 and 12 months after surgery; P 0.05). Sexual function score did not correlate with satisfaction. In the low-interest group (n = 56), satisfaction correlated with high urinary function and urinary bother scores over time (urinary function: 3 and 6 months, urinary bother: at 3, 6 and 12 months postoperatively; P 0.05). Neither sexual function nor sexual bother correlated with satisfaction postoperatively in the low-interest group.The impact of urinary and sexual functions and bothers on patients' overall satisfaction differed between patients with high- and low-interest in sex. The patient's interest in sex should be considered when assessing satisfaction after robot-assisted radical prostatectomy.

In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT-PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem-like cells.

Objectives To identify antigenic peptides of cancer stem-like cells (CSCs) antigen, DNAJB8, and establish a mouse CSCs-targeting immunotherapy model. Materials and methods To induce DNAJB8-specific immune reaction, we stimulated human CD8+ lymphocytes with antigen-presenting cells pulsed with a cocktail of three candidate HLA-A*24:02 restricted peptides and assessed peptide specific human cytotoxic T lymphocytes (CTLs) induction. One of the antigenic peptides showed identical amino acid sequence as corresponding mouse DNAJB8. We evaluated CTL induction with the peptide immunization in mouse model. Results We confirmed peptide-specific interferon-γ secretions and cytotoxic activities of induced human CTLs. In vivo immunization with the peptide to mice, peptide-specific CTL response could be observed in mouse CD8+ T cells. Furthermore, immunization with the peptide showed significant anti-tumor effects compared with negative controls. Conclusion DNAJB8-derived peptide is a novel candidate for CSCs-targeting immunotherapy, and mouse models can be used to evaluate CSCs-targeting immunotherapy.

We report a case of renal transplantation using a horseshoe kidney from a living, genetically unrelated donor. The recipient was a 60-year-old man with diabetic nephropathy, and the donor was the 63-year-old wife of the recipient with a horseshoe kidney free of complications. Computed tomography showed two renal arteries and one renal vein on the left side, and the isthmus was perfused by several accessory arteries and veins. To demarcate the boundary of the isthmus, the left renal artery was ligated and cannulated for in situ perfusion. Furthermore, the isthmus was clamped, and the boundary of the isthmus was confirmed. The kidney was divided at the left margin of the perfused boundary. The cut ends of the isthmus were closed by sutures. The left kidney was transplanted into the right iliac fossa of the recipient. Asymptomatic fluid collection occurred on the cut surface at the isthmus of the donor, and this fluid decreased in due course. On the other hand, the recipient experienced no surgical complication or rejection, while maintaining serum creatinine levels of 2.00–2.20 mg/dL over a 22-month follow-up period. Horseshoe kidneys may be used for transplantation in selected cases after a detailed preoperative evaluation.

Objective To validate two prediction models (European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment) for recurrence and progression of non-muscle invasive bladder cancer in Japanese patients who underwent bacillus Calmette–Guerin instillation therapy. Methods From March 1985 to April 2007, data were analyzed from 366 patients who underwent transurethral resection of bladder tumor followed by bacillus Calmette–Guerin instillation therapy. The ability of two scoring models to predict recurrence and progression was assessed by concordance index. Results For recurrence probability, the concordance index of the European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.514 and 0.576, respectively, which was lower than that (0.604) of a selected single prognostic factor (age) by our multivariate analysis. For progression probability, the concordance index of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.693 and 0.764, respectively, which was higher than that (0.633) of a selected single factor (T stage) by our multivariate analysis. The Spanish Urological Club for Oncological Treatment scoring system resulted in better stratification of tumor recurrence and progression when compared with the European Organization for Research and Treatment of Cancer model, probably because more patients underwent bacillus Calmette–Guerin treatment in the Spanish Urological Club for Oncological Treatment cohort than in the European Organization for Research and Treatment of Cancer cohort. Conclusions The Spanish Urological Club for Oncological Treatment scoring system is a good predictor of tumor recurrence and progression in Japanese patients who underwent bacillus Calmette–Guerin immunotherapy. A large prospective study is warranted to confirm the efficacy of this system.

Background While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy. Methods This study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis. Results PSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS. Conclusions Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined by their abilities of tumor initiation, self-renewal and differentiation. In a previous study, we showed by gene knockdown using siRNA and gene overexpression experiments that Dnaj (Hsp40) homolog, subfamily B, member 8 (DNAJB8), a role in the maintenance, of renal cell carcinoma CSCs/CICs. In the present study, we established Dnajb8 knockout (KO) renal cell carcinoma (RCC) line cells (RenCa cells) and analyzed the cells to confirm the function of Dnajb8 in RCC CSCs/CICs. Dnajb8 KO cells showed reduced ratios of side population cells and reduced sphere forming ability. An in vivo single cell tumor initiation assay revealed that the numbers of CSCs/CICs were 3 in 4 wild-type RenCa cells and 1 in 4 Dnajb8 KO cells. Dnajb8 KO cells showed sensitivity to Docetaxel. On the other hand, Dnajb8 KO cells did not show any sensitivities to stresses including low pH, low glucose, heat shock and sensitivity to cisplatin. The results indicate that Dnajb8 has a role in tumor initiation, side population ratio and sphere formation but it is dispensable for stress responses.

In this paper, the structural and spectroscopic properties of rhodamine 3B (R3B) cations incorporated into titanate nanosheet (TNS)/decyltrimethylammonium (C10TMA) cation hybrid was investigated in...

Leakage of cryogenic fluid can bring diverse consequences within confined environment like FLNG. In particular, leakage from pressurized refrigerant system is expected to form cryogenic pool, which could initiate brittle fracture of the structure as well as violent evaporation of flammable gas. The authors put the series of different leakage scenarios under light and quantitatively analyzed the potential consequences in an attempt to provide overall pictures of this hazard yet to have been made clear so far. Further, use of brittle fracture arresting steel – a new strain of carbon steel produced through special TMCP technology – was explored on its potential to mitigate the risk.

INTRODUCTION AND OBJECTIVES: Cancer stem-like cells (CSCs) are small population of cancer cells with superior tumor initating, seilf-renewel, and differentiation properties. In the previous study, we found that HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma(RCC). HSF1 has been described to induce heat shock proteins by heat shock stress and be related to initiation and progression of cancer. In this study, we investigated the relations of HSF1 and CSC phenotype including DNAJB8. METHODS: RCC cell lines ACHN was given heat shock by incubating in 45 degrees for 60 minutes. HSF1 and DNAJB8 expression was evaluated by RT-PCR and Western blot analysis. CSCs were isolated by side population method by flowcytometry. SP(side population) cells mean CSCs, MP(main population) cells mean non-CSCs. As an inhibitor of HSF1, temsirolimus (mTOR inhibitor) was used. The cell viability was assessed by MTT assay. RESULTS: Heat shock stress enhanced the expression of DNAJB8 as well as SOX2. The expression of these molecules reached maximum 24 hours after heat shock, and the SP population increased at the same time. When MP cells sorted by flowcytometry were stimulated by heat shock, SP population could be newly detected. This fact implies that heat shock stress could induce the reversion from MP cells to SP cells. Concerning the mechanism of the reversion from MP cells to SP cells by heat shock, HSF1 seems to play an important role. We found that the expression of phosphorylated HSF1 increased by heat shock, although the expression level of HSF1 itself did not change. Interestingly, when HSF1 was knocked down by siRNA, DNAJB8 could not be induced even after heat shock stress. This suggests that the stress-inducible expression of DNAJB8 is regulated by HSF1, which bind to the heat shock element(HSE) in the promoter of DNAJB8 gene and stimulate its transcription. Treatment with temsirolimus to ACHN cells could inhibit phosphorylation of HSF1, followed by down regulation of DNAJB8, resulting in the decrease of SP population. SP cells were more susceptible by temsilolimus treatment than MP cells. CONCLUSIONS: Stress including heat shock such as hyperthermia might induce DNAJB8 expression, which is related to CSC phenotype. Phosphorylation of HSF1 is required in this process. mTOR inhibitor could inhibit CSC specifically by inhibiting phosphorylation of HSF1.

Purpose: Administration of anticancer drugs may damage gastrointestinal epithelium, thereby increasing the permeability of the gastrointestinal mucosa. We estimated the usefulness of oral lactulose and mannitol (L/M) test for assessment the extent of mucosal damage following postoperative chemotherapy for human malignant disease. Methods: The permeability index (PI): the urinary recovery ratio of excreted L to M was measured before and after chemotherapy in 31 patients with gastrointestinal cancers who underwent surgical resection. These findings were compared with data on 12 patients with breast cancer. The effect of chemotherapy was evaluated by the ratio of increase in PI, which was designed as post-chemotherapy value on day 7 divided by pre-chemotherapy value. Results: The mean PIs before chemotherapy in patients who underwent gastrectomy or colectomy were significantly higher than the value in those treated with mastectomy (p < 0.05). In the gastrointestinal cancer patients, the mean PIs significantly increased after chemotherapy compared with the pre-chemotherapeutic value (p < 0.01), however no significant difference was seen in breast cancer patients. When the ratios of increase in PI were calculated among gastric cancer patients, the total gastrectomy group showed a significantly higher increase in PI compared with the partial gastrectomy group (p < 0.05). Conclusions: Since the oral L/M absorption test is useful for assessing the degree of mucosal damage and measurement of intestinal permeability, this analysis should be recommended to determine the optimum timing and the adequate dosage of the anticancer drug administration.

In order to prevent harmful vibration in ships at the early stage of design, anti-vibration design is required on the basis of accurate estimation methods. To investigate vibration response of superstructure, very large scale of 3-dimensional finite element analysis including hull structure is sometimes conducted, however, significant improvement of accuracy is not yet achieved due to the difficulty in estimating damping. More advanced treatment of damping is necessary to obtain more accurate vibration responses.In the 1st report, a new identification method of damping factor is proposed by calculating dynamic response directly on the basis of Rayleigh's damping [C]=α[M]+β[K]. Then the capability of this method is verified by the measured data of frame structure model. The 2nd report relates that this method is applied to the measured data of a 280, 000DWT VLCC's superstructure and that its ability is confirmed.In this 3rd report, Rayleigh's damping is enhanced to the form of [C]=αs[MS]+αw[Mw]+β[K] where αs and αw are the identified coefficients corresponding to the mass matrix of structure and the virtual mass matrix of fluid, respectively. To verify the above assumption, following tests and identifications are carried out: 1) Exciter test of model ship is conducted in air condition and in water condition to measure transfer function. Firstly, αs and β are identified for model ship in air. Using the same αs and β, transfer function in water is identified by αw considering that the difference of transfer functions between in air and in water caused by the increase of fluid damping. Simulated transfer functions in water by these three identification coefficients show good agreement with the measured ones. 2) Exciter test of actual VLCC3) is utilized to identify three coefficients. Same αw as of model ship is taken in the identification on the assumption that the coefficient of fluid damping of VLCC is approximately similar to that of model ship, αs and β are identified for VLCC in ballast condition. Then transfer functions in ull load condition is estimated by these three parameter obtained in ballast condition, which coincide with the measured data.

It is important to prevent excessive vibration in the superstructure of a ship, in order to provide comfortable habitability to ship's crew and to keep normal operative condition for navigation instruments. Vibrations observed in ships has the following features :(1) The vibration amplitude largely scatters as long as the vibration is induced by the propeller, because propeller exciting force fluctuates due to the change of flow velocity into the propeller.(2) The vibration does not always have a single frequency but have several frequencies, since there are several exciting sources in a vessel such as main engine, propeller and auxiliary machines.Therefore, the vibration of ship's superstructure cannot be reduced by installing a simple anti-vibrating device, but more sophisticated instrument is required.To satisfy the above requirement, an active mass damper driven by electromagnetic force has been developed. An active mass damper can reduce effectively the vibration of fluctuating amplitude as well as the combined frequencies induced by several vibration sources. Firstly, vibration characteristics of this damper were confirmed by the exciter test using model frame structure. Then the capability of the damper was verified by the measurement of a VLCC and a large bulk carrier. Vibration amplitude of these vessels were confirmed to be reduced to about 1/2 to 1/5 of the original level by this active mass damper.

We examined p53 protein stability and DNA damage-induced p53-dependent responses in a human leukemic CEM cell line and two teniposide-resistant sublines, CEM/VM-1 and CEM/VM-1-5 ( approximately 40 and 400-fold resistant to teniposide, respectively). Although all cell lines contain the same p53 mutations at codons 175 (Arg--His) and 248 (Arg--Gln), the constitutive levels of p53 were progressively increased with the resistance of the cells to teniposide. By pulse-chase experiments, we found that the half-lives of mutant p53 protein were approximately 12, 17, and30 h in CEM, CEM/VM-1, and CEM/VM-1-5 cells, respectively. The prolonged half-lives of p53 in these cells is consistent with the fact that the protein harbors the indicated mutations. Of note, however, is the fact that the increased p53 protein half-lives in the two drug-resistant cell lines corresponds to a proportional decrease in MDM2 protein levels but an increase in p53-MDM2 binding interactions. This suggests that MDM2-mediated p53 degradation may be altered in our leukemic cell lines. The DNA damage-induced p53 response is fully functional in the drug-sensitive CEM cells containing a mutant p53, but this pathway is attenuated in the drug-resistant cells. Specifically, while the mutant p53 was phosphorylated at serine-15 in response to ionizing radiation in all these cell lines, mutant p53 induction in response to teniposide or ionizing radiation and induction of the p53-target genes, p21 and GADD45 only occurred in the drug-sensitive CEM cells. As assessed by MTT cytotoxicity assay, CEM cells were also significantly more sensitive to ionizing radiation, compared to the drug-resistant cell lines, and this correlated with p53 induction. Collectively, these results suggest that changes in constitutive mutant p53 protein levels, p53-MDM2 binding interactions, and altered regulation of the DNA damage-inducible p53-dependent pathway may play a role in drug- and radiation-responsiveness in these cells.

BACKGROUND Mutations of p53 can lead to the production of anti-p53 antibodies in sera of cancer patients. Before this study, the value of preoperative serum anti-p53 antibodies in determining the prognoses of patients with gastric carcinoma had yet to be determined. METHODS The authors used a highly specific enzyme-linked immunosorbent assay (ELISA) kit (Pharma Cell, France) to determine the preoperative presence of serum anti-p53 antibodies in 120 patients with gastric carcinoma. The relation between the positivity of serum anti-p53 antibodies and p53 abnormal staining of gastric carcinoma tissues was examined. Clinicopathologic characteristics and prognoses of these patients were given attention. RESULTS Anti-p53 antibodies were detected in 19.2%(23 of 120) of these patients with gastric carcinoma. Among those who were positive for anti-p53 antibodies, female patients were predominant, the depth of invasion was greater, and liver metastasis was present, as compared with those who were negative for anti-p53 antibodies. Regarding other factors, there were no differences between those who were positive or negative for anti-p53 antibodies. Gastric carcinoma tissues had a 60.9%(14 of 23) positivity rate of p53 staining with anti-p53 antibodies and a 33.0%(32 of 97) negativity rate, and this difference was statistically significant (P < 0.05). The survival time of patients with anti-p53 antibodies in their sera was shorter than that of subjects with sera negative for anti-p53 antibodies (P < 0.05). The presence of anti-p53 antibodies was not an independent prognostic factor in multivariate analysis. CONCLUSIONS Serum assay of anti-p53 antibodies is a rapid and readily facilitated test for predicting tumor advancement, depth of invasion, and liver metastasis, and it will show a poorer prognosis for surgically treated patients with gastric carcinoma. Cancer 1999;85:302–8. © 1999 American Cancer Society.

The interaction of cis -1,1-cyclobutanedicarboxylato(2R)-2-methyl-1,4-buta-nediammineplatinum(II) (NK121) and ds-diammme(glycolato)platinum(II) (254-S), analogues of cis<

In 58 human gastric cancers, the expression of P-glycoprotein (P-gp) was evaluated immunohistochemically and chemosensitivity was determined using the in vitro succinate dehydrogenase inhibition (SDI) test. Tumors which contained over 75% stained cells were scored as positive, and 14 of 58 cases (24%) were positive. There was no significant correlation between P-gp expression and clinicopathologic features. The succinate dehydrogenase (SD) activity for each drug of P-gp positive and negative tumors was as follows: 81.8 ± 15.2% vs. 66.3 ± 16.1% for Adriamycin (ADM), 75.5 ± 14.2% vs. 59.1 ± 17.6% for aclacinomycin A (ACR), 71.7 ± 15.0% vs. 61.1 ± 14.0% for mitomycin C (MMC), and 57.5 ± 18.4% vs. 47.0 ± 16.7% for cisplatin (CDDP). The increase in SD activity was evident in P-gp positive tumors compared with negative ones in cases of ADM (P = 0.0044), ACR (P = 0.0105), and MMC (P = 0.0353). We suggested that P-gp expression is closely related to chemosensitivities of human gastric cancers to anthracyclines. © 1994 Wiley-Liss, Inc.

Recent studies have shown that microsatellite instability (MSI) play an important role in the development of various types of cancer. To clarify the clinicopathologic significance of MSI in colorectal carcinoma (CRC), the presence of MSI was examined in 54 Japanese cases of CRC using the polymerase chain reaction-based method. The incidence of MSI in CRC cases was 13 out of 54 cases (24%). CRC with MSI also showed a significant tendency not to have lymph node metastasis (P

Background. Expression of sialyl Tn antigen (STN) or serum STN levels were reported to be the independent prognostic factors of colon and ovarian cancers, respectively. The clinical significance of serum STN was evaluated as a tumor marker in gastric cancer. Methods. Preoperative STN levels were examined in 350 patients with gastric cancer, surgically treated in the Department of Surgery II. Kyushu University Hospital, and in the National Kyushu Cancer Center, between April, 1981 and April, 1986. The patients were divided into two groups: a high STN group (n = 304), with over 45 U/ml of STN, and a low STN group (n = 46), with less than or equal to 45 U/ml. Results. In the high STN group, the patients were older and the tumors were larger, compared to the low STN group. Histologically, tumors in the high STN group were deeply penetrating and the rates of lymphatic involvement, vascular involvement, and lymph node and hepatic metastases were higher. Infiltrative growth patterns dominated. Thus, the tumors were in an advanced stage. The 5-year survival rate for patients in the high STN group was significantly less than that of patients in the low STN group (44.8% ± 7.9% versus 75.1% ± 2.6%, P < 0.05). Conclusions. Because a high STN level correlates with an advanced tumor stage and a poorer prognosis, close follow-up and aggressive therapy are recommended.

cis-1,1-Cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammin eplatinum(II) (NK121) and cis-diammine(glycolato)platinum (254-S), analogues of cis-diamminedichloroplatinum (II) (CDDP) with reduced nephrotoxicity, are under clinical phase trial in Japan. Since CDDP has been shown to be more cytotoxic under conditions of an elevated temperature, we tested the cytotoxicity and cellular uptake of these analogues at 37 degrees and 43 degrees C using EMT6/KU cells in vitro. The cytotoxicity of CDDP was enhanced at 43 degrees C, and that of NK121 and 254-S was also enhanced, in a dose- and time-dependent manner. The 90% cytotoxic concentration (IC90) of each drug was reduced 2.9-fold for CDDP, 2.5-fold for NK121, and 2.2-fold for 254-S. Cytotoxicity was maximal when the two modalities were used simultaneously for all three drugs. The intracellular platinum concentration was assayed using flameless atomic absorption spectrophotometry. When exposed to IC90 drug concentration at 43 degrees C for 2 h simultaneously, the intracellular platinum concentration increased to 0.095 +/- 0.007 micrograms/10(7) cells (a 1.9-fold increase) for CDDP, to 0.198 +/- 0.012 micrograms/10(7) cells (a 1.3-fold increase) for NK121, and to 0.090 +/- 0.014 micrograms/10(7) cells (a 1.3-fold increase) for 254-S; respectively, as compared with the level measured after drug exposure at 37 degrees C (P0.05 for all drugs). The elevation in platinum concentration may be one of mechanism related to a synergistic effect of the two treatment modalities. The concomitant use of CDDP analogues and heat shows potential for possible clinical application.

The relationship between postoperative chemotherapy and survival time after gastric resection in patients with advanced gastric cancer was examined by retrospectively reviewing data on 916 patients treated in our clinics between 1965 and 1985. Of these patients, 738 were treated postoperatively with antitumor drugs. Postoperative chemotherapy was more often prescribed for those in the advanced stages of malignancy. Univariate analysis revealed that the survival time of patients given postoperative chemotherapy was shorter than for those not receiving chemotherapy, but there was no statistical significance. Multivariate analysis using the Cox regression analysis adjusted for sex, age, and other covariants indicated that operative curability, liver metastasis, serosal invasion, lymph node metastasis, peritoneal dissemination, and tumor size were the important prognostic factors. There was no correlation with postoperative chemotherapy. Our findings rule out any relationship between postoperative chemotherapy and length of survival time for patients with advanced gastric cancer undergoing gastric resection.

The in vitro drug sensitivity of gastric cancer tissues obtained from 40 patients with advanced cancer was compared in terms of the pathological classifications which were assigned according to the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan. Cases of poorly differentiated adenocarcinoma which had penetrated the serosa were evaluated using the succinate dehydrogenase inhibition (SDI) test for determining the in vitro chemosensitivity. The sensitivity of the stage III group to cisplatin was higher than that of the stage IV group. Although there were no statistical differences in drug sensitivities according to macroscopic findings (Borrmann's classification), the expanding growth type was more susceptible that the infiltrating type to cisplatin, aclacinomycin A (ACR) and carboquone (CQ) microscopically. In cases of lymph node metastasis [n(+)] the sensitivity to cisplatin, ACR, CQ, adriamycin and mitomycin C was less than in those with or without primary lymph node metastasis [n(-)]; lymphatic invasion in the gastric wall (ly) was a significant factor linked to drug resistance. Our findings indicate that the evaluation of tumor pathology is important in predicting the chemosensitivity of poorly differentiated gastric cancers.

An active mass damper has been developed to reduce the vibration occured in ships especially in the superstructures.Active mass damper was designed so as to reduce effectively the vibration of fluctuating frequency and amplitude induced by several vibration sources such as main engine and propeller as well as the steady vibration of single frequency and amplitude.Vibration characteristics were confirmed by the experiment with the aid of model structure. Then the active mass damper was applied to 150, 000 DWT tanker to verify the efficiency of reducing vibrations, and obtained satisfactory results. In this paper, (1) The active mass damper reduced the vibration of the superstructure of the 150, 000 DWT tanker especially in the resonance peak area. The vibration due to unbalanced moment decreased to one sixth of its original level, vibration derived from propeller exciting force to one half and vibration induced by main engine exciting force to one fifth, simultaneously.(2) The active mass damper can be applied to not only the vibration of superstructure of ship but local vibrations of various part.

In this letter, a new self-organizing map (SOM) algorithm with computational cost O(log2 M) is proposed where M2 is the size of a feature map. The first SOM algorithm with O(M2) was originally proposed by Kohonen. The proposed algorithm is composed of the subdividing method and the binary search method. The proposed algorithm does not need the neighborhood functions so that it eliminates the computational cost in learning of neighborhood vectors and the labor of adjusting the parameters of neighborhood functions. The effectiveness of the proposed algorithm was examined by an analysis of codon frequencies of Escherichia coli (E. coli) K12 genes. These drastic computational reduction and accessible application that requires no adjusting of the neighborhood function will be able to contribute to many scientific areas.

Disseminated carcinimatosis of the bone marrow is accompanied by solid tumors, and gastric cancer accounts for the majority. The prognosis of this condition is poor, however, the pathogenesis for wide-spread bone lesions has yet to be elucidated. In 9 patients with gastric cancer demonstrating disseminated carcinomatosis of the bone marrow, the characteristic clinicopathological features were examined. Immunohistochemistry for receptor activator of NF-kappaB ligand (RANKL) and parathyroid hormone-related protein was also performed on gastric cancer tissue and bone marrow specimens to identify the factors responsible for the occurrence of bone lesions in patients presenting with this condition. The characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer include a yonger patient age, an elevation of serum alkaline phosphatase and/or lactate dehydrogenase levels, wide-spread bone metastases with osteolytic bone destruction, a low incidence of hypercalcemia and a histological gastric cancer type of either signet ring cell carcinoma or poorly diffentiated adenocarcinoma. The expression of RANKL, which is one of the master regulators of osteoclastic bone resorption in bone metastasis, was also found in gastric cancer cells obtained from such patients. The RANKL expressed in gastric cancer may therefore play a critical role in the promotion of osteoclast formation, which has been suggested to be involved in the pathogenesis of bone lesions.

Metastasis-associated protein MTA1 and histone deacetylase form a protein complex with histone deacetylase activity that plays an important role in histone deacetylation, alteration of chromatin structure and transcriptional control. The precise role of the MTA1 protein in the malignant progression of human cancers remains unknown, however, especially its overexpression and relationship with histone acetylation/deacetylation in experimental and clinical tumors. The expression levels of MTA1 protein and the acetylation levels of histone H4 were examined in 70 cases of surgically resected esophageal squamous cell carcinomas, using immunohistochemistry. The intensities of immunostaining of MTA1 protein and acetylated histone H4 in carcinoma tissues (Ca) were compared to normal epithelium (N) contained in the same section. Thirty of 70 cases (42.9%) displayed overexpression of MTA1 protein (N < Ca). Cancers overexpressing MTA1 protein invaded deeper into the esophageal wall (p < 0.005) and showed significantly higher degrees of lymph node metastasis (p < 0.01), higher pathological stage, more lymphatic involvement and poorer prognosis (p < 0.05) than the remaining cases. The acetylation levels of histone H4 inversely correlated to the depth of cancer invasion and pathological stage (p < 0.05), and the patients with higher level of histone H4 acetylation had a better prognosis (p < 0.05). Furthermore, immunostaining patterns of MTA1 and acetylated histone H4 were inversely correlated (p < 0.001), demonstrating the relationship of deacetylation of histone H4 in MTA1-overexpressing carcinomas. In conclusion, the data suggest that the overexpression of MTA1 protein and acetylation level of histone H4 protein, both of which are closely related, might be useful predictors of malignant potential of esophageal squamous cell carcinomas. Thus, strategies involving inhibition of MTA1 function as well as inhibition of histone deacetylation could be novel approaches for the treatment of esophageal squamous cell carcinomas. © 2004 Wiley-Liss, Inc.

To determine the role of adenomatous polyps in the development of colorectal cancers, we examined the relationship between the distribution and polyps with different grades of dysplasia (low, high), or/and cancers in the colorectum.The distribution of 527 polyps with low-grade dysplasia was compared with that of 121 polyps with high-grade dysplasia, and 10 colorectal cancer lesions with adenomatous polyps in 361 patients who underwent total colonoscopy.The distribution rate of polyps at the distal colon and rectum into polyps with high-grade dysplasia significantly increased in comparison to that into polyps with low-grade dysplasia, respectively (p0.002). The percentage of polyps with high-grade dysplasia measuring1 cm significantly increased in comparison to that with low-grade dysplasia measuring1 cm (p0.00001). In patients with both adenomatous polyps and colorectal cancers, the polyps with high-grade dysplasia at the distal sites of cancerous lesions increased significantly more than at the proximal sites of cancerous lesions (p0.05). Polyps with high-grade dysplasia have malignant potentials to intermediate between polyps with low-grade dysplasia and colorectal cancers in our study.The different distributions of different grades thus suggested that polyps with different grades of dysplasia at various colorectal sites were found to have different malignant potentials for cancer development.

Introduction and objective Human Equilibrative Nucleoside Transporter 1 (hENT1) and Ribonucleotide reductase M1 (RRM1) play important roles in pharmacokinetics of gemcitabine, and excision repair cross-complementing 1 (ERCC1) is related to drug resistance to CDDP. We evaluated the expression level of these molecules in patients with metastatic bladder cancer treated with gemcitabine—cisplatin (GC)-based chemotherapy. Methods Clinical data were retrieved from the databases from May 2002 to October 2011 in 40 patients (age 35–88; male 36; female 4) with advanced bladder cancer treated by GC (Gemcitabine + Cisplatin) regimen (17 patients) and GCT (GC + Paclitaxel) regimen (23 patients). Inclusion criteria for this study were clinically and/or histologically documented advanced and/or metastatic (stage 4) bladder cancer. We carried out immunohistochemical staining chemo-naive primary bladder tumor specimens with specific hENT1, RRM1 and ERCC1 antibodies. Pathologist blinded to clinical outcomes evaluated the expression level of these molecules. The clinical and histopathological data were analyzed to evaluate predictive factors. Results With regards to anti tumor response, high hENT1 expression group showed better clinical response comparing with low hENT1 expression group (90% versus 35%, P = 0.001). High hENT1 expression group and low RRM1 expression group showed significantly better survival (log-tank test P Conclusions The expression of hENT1 and RRM1 was associated with prolonged survival in patients with metastatic bladder cancer treated with GC-based chemotherapy. The combined analysis of hENT1 and RRM1 expression can be a promising biomarker which can predict the clinical response and the prognosis of patients with advanced bladder cancer treated by gemcitabine-based chemotherapy.

We treated a patient with a postoperative local recurrence of gallbladder cancer who showed a long-term response to low-dose 5-fluorouracil (5-FU) and cisplatin (CDDP) therapy. A 60-year-old woman was diagnosed with advanced gallbladder cancer, for which she underwent an extended cholecystectomy, bile duct resection and a partial resection of the duodenum in March 2000. The pathological diagnosis was well differentiated tubular adenocarcinoma of si, ly1, v1, hinf2, binf2, n0. Eight months later, she presented with cholangitis and obstructive jaundice due to a local recurrence of the gallbladder cancer and her serum CA19-9 level had increased to 1,991.6 U/ml. The biliary obstruction was treated by PTCD and a subsequent self-expanding metallic stent. In addition, she was also placed on combined chemotherapy with low-dose 5-FU and CDDP. Her serum CA19-9 level thereafter gradually decreased, so that after eight months it was within the normal range, and the recurrent tumor at the hepatic hilus was also observed to have decreased in size on the CT scan. As of this writing she has undergone eight courses of low-dose 5-FU and CDDP therapy over about a year and has been able to maintain a good quality of life without any severe adverse effects.

We report here gastric metastasis from lung carcinoma in an 80-year-old man. His chief complaint was epigastric pain from metastases in the stomach. Although metastasis from primary carcinoma of the lung to the small intestine is more common than has been previously suspected, symptoms are rare. Such a metastasis may present as bowel perforation. To find cases of lung carcinoma metastasis to the gastrointestinal tract is clinically rare, and there have been few reports in the English literature. This report describes the gastrointestinal metastasis from lung carcinoma.