Risk of prostate cancer in African-American men: Evidence of mixed effects of dietary quercetin by serum vitamin D status.

BACKGROUND: African-American (AA) men experience higher rates of prostate cancer (PCa) and vitamin D (vitD) deficiency than white men. VitD is promoted for PCa prevention, but there is conflicting data on the association between vitD and PCa. We examined the association between serum vitD and dietary quercetin and their interaction with PCa risk in AA men. METHODS: Participants included 90 AA men with PCa undergoing treatment at Howard University Hospital (HUH) and 62 controls participating in HUH's free PCa screening program. We measured serum 25-hydroxy vitD [25(OH)D] and used the 98.2 item Block Brief 2000 Food Frequency Questionnaires to measure dietary intake of quercetin and other nutrients. Case and control groups were compared using a two-sample t-test for continuous risk factors and a Fisher exact test for categorical factors. Associations between risk factors and PCa risk were examined via age-adjusted logistic regression models. RESULTS: Interaction effects of dietary quercetin and serum vitD on PCa status were observed. AA men (age 40-70) with normal levels of serum vitD (>30 ng/ml) had a 71% lower risk of PCa compared to AA men with vitD deficiency (OR = 0.29, 95%CI: 0.08-1.03; P = 0.055). In individuals with vitD deficiency, increased dietary quercetin showed a tendency toward lower risk of PCa (OR = 0.91, 95%CI: 0.82-1.00; P = 0.054, age-adjusted) while men with normal vitD were at elevated risk (OR = 1.23, 95%CI: 1.04-1.45). CONCLUSION: These findings suggest that AA men who are at a higher risk of PCa may benefit more from vitD intake, and supplementation with dietary quercetin may increase the risk of PCa in AA men with normal vitD levels. Further studies with larger populations are needed to better understand the impact of the interaction between sera vitD levels and supplementation with quercetin on PCa in AA men.

Endoscopic closure of colonic fistulas in colon cancer patients using a combination of hemoclips and endoloops: two case reports.

Chronic colon fistulas, which commonly result from operative complications, are generally managed surgically. We present an endoscopic technique of fistula closure that involves the combined use of hemoclips and endoloops. Two consecutive patients with colonic fistulas that were refractory to conservative treatment were successfully managed with this new endoluminal technique. This minimally invasive treatment modality affords accurate localization of the fistula orifice and results in a low mortality and morbidity rates.

Age and sex differences in the incidence of esophageal adenocarcinoma: results from the Surveillance, Epidemiology, and End Results (SEER) Registry (1973-2008).

Risk factors driving sex disparity in esophageal cancer are unclear. Recent molecular evidence suggests hormonal factors. We conducted a national descriptive epidemiological study to assess the hypothesis that estrogen exposure could explain the male predominance in observed esophageal adenocarcinoma incidence. We analyzed the esophageal cancer incidence trends by histology and sex from 1973 to 2008 in nine population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) 9 Registry Database. We used age as a proxy for estrogen exposure in females. The collective age groups annual percentage change in esophageal adenocarcinoma for females is positive (0.03%; 95% confidence interval: 0.02, 0.03%) during the study period. Interestingly, the esophageal adenocarcinoma annual percentage change in incidence rates for females during the same time period is significantly negative from ages 50-54 to ages 60-64. Even though the incidence of esophageal adenocarcinoma rises in both males and females, the male-to-female ratio across age peaks in the 50-54 years then decreases. Furthermore, the esophageal adenocarcinoma age-adjusted incidence rate in postmenopausal females age 80 and above increases with age unlike their male counterparts. Taken together, these data support the hypothesis that the endocrine milieu in pre- and perimenopausal females serves as a protective factor against esophageal adenocarcinoma, and with loss of estrogen or because of the increasing time period away from estrogen exposure, the rate of esophageal adenocarcinoma incidence increases in the older postmenopausal female. Because females comprise the largest portion of the elderly population with esophageal adenocarcinoma, these findings are significant.

Induction of high-titer IgG antibodies against multiple leukemia-associated antigens in CML patients with clinical responses to K562/GVAX immunotherapy.

The ability to target myeloid leukemia with immunotherapy would represent a significant therapeutic advance. We report here immunological analysis of clinical trials of primary and secondary vaccination with K562/GM-CSF immunotherapy in adult chronic phase chronic myeloid leukemia patients (CML-CP) with suboptimal responses to imatinib mesylate. Using serological analysis of recombinant cDNA expression libraries of K562 with autologous vaccinated patient serum, we have identified 12 novel chronic myeloid leukemia-associated antigens (LAAs). We show that clinical responses following K562/GM-CSF vaccination are associated with induction of high-titer antibody responses to multiple LAAs. We observe markedly discordant patterns of baseline and induced antibody responses in these identically vaccinated patients. No single antigen was recognized in all responses to vaccination. We demonstrate that an additional 'booster' vaccination series can be given safely to those with inadequate responses to initial vaccination, and is associated with more frequent induction of IgG responses to antigens overexpressed in K562 vaccine compared with primary CML-CP. Finally, those with induced immune responses to the same LAAs often shared HLA subtypes and patients with clinical responses following vaccination recognized a partially shared but non-identical spectrum of antigens; both findings have potentially significant implications for cancer vaccine immunotherapy.

Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer.

BACKGROUND: This study was aimed to detect post-chemotherapeutic circulating tumour cells (CTCs) in stage III colon cancer patients and identify those who were at high risk of relapse. METHODS: We used human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) as the biomarkers to detect CTCs in 90 stage III colon cancer patients undergoing curative resection followed by mFOLFOX chemotherapy. RESULTS: Post-chemotherapeutic relapse occurred in 30 (33.3%) patients. By univariate analysis and multivariate proportional hazards regression analysis, perineural invasion (hazard ratio (HR): 2.752; 95% confidence interval (CI): 1.026-7.381), high post-chemotherapeutic serum CEA levels (HR: 2.895; 95% CI: 1.143-7.333) and persistent presence of post-chemotherapeutic CTCs (HR: 6.273; 95% CI: 2.442-16.117) were independent predictors of post-chemotherapeutic relapse. In addition, the persistent presence of post-chemotherapeutic CTCs strongly correlated with reduced disease-free survival and overall survival. Accuracy of detecting relapse in post-chemotherapeutic stage III colon cancer patients by analysing the persistent presence of post-chemotherapeutic CTCs was higher than that by post-chemotherapeutic CEA levels (odds ratio: 50.091 vs 5.211). CONCLUSION: The persistent presence of post-chemotherapeutic CTCs is a potential powerful surrogate marker for determining clinical outcome in stage III colon cancer patients receiving adjuvant mFOLFOX chemotherapy.

Intraoperative anastomotic dye test significantly decreases incidence of anastomotic leaks in patients undergoing resection for rectal cancer.

BACKGROUND: Anastomotic leakage is still a major complication in colorectal surgery. Prompt recognition and immediate treatment of anastomotic leak during surgery may reduce postoperative morbidity and mortality. Various types of intraoperative anastomotic test have been proposed to reduce the incidence of this complication. The aim of this study was to assess our experience with intraoperative dye test in rectal cancer surgery. METHODS: Between 2006 and 2009, a retrospective review of a single general surgeon's practice identified 76 patients who underwent the intraoperative dye test in rectal cancer surgery. Seventy-three of these 76 patients underwent elective surgery without creation of a diverting stoma. Diluted dye was routinely introduced into the rectal lumen to test anastomotic integrity. Intraoperative leak was repaired prior to the completion of the procedure. No routine radiological survey assessed anastomotic integrity postoperatively. RESULTS: In 11 (14.5 %) out of 76 patients, anastomotic leaks were found and treated intraoperatively. None of the 65 patients without intraoperative leaks developed clinical leaks during the follow-up period. Postoperative leakage only occurred in one patient (1.3 %). He developed pelvic abscess evidenced by abdominal computed tomography scan and was treated non-operatively. CONCLUSIONS: The favorable results allow the authors to recommend the routine use of the intraoperative dye test for colorectal anastomoses.

Prospective analysis of KRAS wild-type patients with metastatic colorectal cancer using cetuximab plus FOLFIRI or FOLFOX4 treatment regimens.

Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, has proven to be efficient in the treatment of metastatic colorectal cancer. We made a prospective study of the efficacy and toxicities of cetuximab-combination first-line (FOLFOX4) versus second/third-line (FOLFIRI) chemotherapy in 98 KRAS wild-type patients who had metastatic colorectal cancer. Wild-type KRAS had been identified by direct sequencing. Associations between clinical response/progression-free survival/overall survival/toxicities and cetuximab-combination chemotherapy timing were evaluated. The overall response rate was significantly higher for first-line treatment than for second/third-line treatment (relative risk = 1.707, 95% confidence interval = 1.121-2.598). Both progression-free survival and overall survival indicated significantly longer survival of first-line treatment than second/third-line treatment patients. This study is a validation of a molecular analysis of KRAS wild-type status for the prediction of response to cetuximab-combination chemotherapy for metastatic colorectal cancer patients; its predictive role was less prominent in the second/third-line than in the first-line treatment patients.

Molecular detection of persistent postoperative circulating tumour cells in stages II and III colon cancer patients via multiple blood sampling: prognostic significance of detection for early relapse.

BACKGROUND: The purpose of this study was to detect postoperative persistent circulating tumour cells (CTCs) in stages II and III colon cancer patients undergoing curative resection and so identify a subgroup of patients who are at high risk for early relapse. METHODS: Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in 141 stages II and III colon cancer patients undergoing curative resection to determine the significance of CTCs in postoperative early relapse. RESULTS: Out of 141 patients, postoperative early relapse and non-early relapse/no relapse was found in 48 (34.0%) patients and 93 (66.0%) patients, respectively. Univariately, postoperative early relapse was significantly correlated with lymph node metastasis (P=0.025), vascular invasion (P=0.002), perineural invasion (P=0.001), laparoscopic surgery (P=0.019), high postoperative serum CEA levels (P=0.001), and presence of persistent postoperative CTCs (P<0.001). Using a multivariate proportional hazards regression analysis, the presence of perineural invasion (P=0.034; HR, 1.974; 95% CI: 1.290-3.861), high postoperative serum CEA levels (P=0.020; HR, 2.377; 95% CI: 1.273-4.255), and the presence of persistent postoperative CTCs (P<0.001; HR, 11.035; 95% CI: 4.396-32.190), were demonstrated to be independent predictors for postoperative early relapse. Furthermore, the presence of persistent postoperative CTCs was strongly correlated with a poorer disease-free and overall survival (both P<0.001). CONCLUSIONS: This study suggests that molecular detection of persistent postoperative CTCs is a prognostic predictor of early relapse in UICC stage II/III colon cancer patients, and thus could help to define patients with this tumour entity for an enhanced follow-up and therapeutic program.

Association between panel reactive antibodies and acute small bowel rejection: analysis of a series of 324 intestinal transplants.

INTRODUCTION: Panel reactive antibodies (PRA) to class I and II HLA molecules have been associated with acute kidney graft rejection, but their role in small bowel transplantation has not been characterized. METHODS: Since 1994, 324 SBT, alone or as multivisceral transplantation (MVT), have been performed in 286 patients. Routine and surveillance biopsies were performed to rule out or confirm acute rejection (AR), and PRA quantification was performed at varying intervals. We obtained data from 110 patients and 651 PRA measurements. While AR grade (mild to severe, grades 1-3) was determined by histopathological analysis, the status of no AR was determined also by clinical data. When biopsy samples or PRA measurements were frequent around an AR episode within periods of 7 days, the highest value was used. RESULTS: A comparison could be made between 259 instances in which there was a PRA measurement and simultaneous rejection evaluation. Positive PRA showed association with AR (P < 0.001). The positive and negative predictive values were 44% and 79%, respectively. No correlation was found in the severity of rejection. CONCLUSION: The presence of increased levels of PRA is a risk factor of rejection in small bowel transplantation. Alloantibody-mediated injury to the graft contributes frequently to acute rejection of small bowel, and it is associated with cell-mediated immunity in variable proportion.

Electron microscopy investigations of V defects in multiple InGaN/GaN quantum wells and InGaN quantum dots.

The mechanism of high emission of InGaN-based multiple quantum wells, which exhibit exceptionally high light emission efficiency despite their high defect density, is still not fully understood. Here, we deal with this problem, showing the details of structure and formation of V defects in the multiple quantum wells and reviewing interpretations proposed so far. Then, we show a structural investigation of three-dimensional high-density quantum dots, fabricated instead of quantum wells in the active layer. The shape and size of the InGaN quantum dots and the SiN(x) masks for the growth of the dots have been revealed using high-angle annular dark field scanning transmission electron microscopy, energy dispersive X-ray spectroscopy nanoanalysis and high-resolution transmission electron microscopy.

Changes in mitochondrial respiratory enzyme activity after ischemia-reperfusion injury in living-donor liver transplantation.

BACKGROUND: Ischemia-reperfusion (I-R) injury plays an important role in the immediate graft function in living-donor liver transplantation (LDLT). There is growing evidence that mitochondria play a pivotal role in I-R injury. Our aim was to evaluate changes in mitochondrial respiratory enzyme activities after I-R injury in LDLT. METHODS: Specimens from 8 donor recipient pairs enrolled in this study were obtained from the donor livers before harvest (before I-R injury) and after vascular anastomosis in the recipient (after I-R injury). Histidine-tryptophan-ketoglutarate solution was used to perfuse the organ during the cold ischemic period between harvesting and transplantation. We correlated changes in mitochondrial respiratory enzyme complex activity (succinate cytochrome c reductase [SCCR]; NADH cytochrome c reductase [NCCR]) after I-R injury with clinical data and graft status. RESULTS: NCCR and SCCR activities did not uniformly decrease after I-R injury. Two of 8 recipients experienced graft dysfunction after transplantation. The decrease in neither NCCR nor SCCR activity correlated with graft dysfunction in these 2 patients. Among the clinical factors, grafts from older donors tended to show decreased NCCR activity after I-R injury. CONCLUSIONS: In this study, changes in mitochondrial respiratory enzyme activity failed to predict the severity of I-R injury in LDLT. The organ preservation solution may play a protective role on mitochondrial respiratory enzymes during I-R injury.

First Report of Cucumber mosaic virus on Vigna marina in Taiwan.

Vigna marina (Burm.) Merr., the dune bean or notched cowpea, is a tropical creeping vine that grows on sand dunes along the coastal regions of Taiwan. Although V. marina is a weed, some varieties are also grown for fodder and food. This legume is a natural host of Bean common mosaic virus in the Solomon Islands (1) and Alfalfa mosaic virus or Beet western yellows virus in Australia (2). In April 2009, plants of V. marina showing severe mosaic and chlorotic ringspots on the foliage were found in the coastal region of Hualien County in eastern Taiwan. Indirect ELISA on a single diseased plant showed positive results with antibodies against the cucumber isolate of Cucumber mosaic virus (CMV) but negative to Broad bean wilt virus-1, Broad bean wilt virus-2, and some potyviruses (Agdia Inc., Elkhart, IN). A pure isolate of CMV was obtained from V. marina through three successive passages of single lesion isolation in sap-inoculated Chenopodium quinoa. Results of mechanical inoculations showed that the CMV-V. marina isolate was successfully transmitted to C. amaranticolor, C. murale, C. quinoa, Chrysanthemum coronarium, Gomphrena globosa, Nicotiana benthamiana, N. tabacum cv. Vam-Hicks, Phaseolus limensis, P. lunatus, P. vulgaris, Tetragonia tetragonioides, V. marina, V. radiata, and V. unguiculata subsp. sesquipedalis. These results of artificial inoculations were confirmed by ELISA. Homologous reactions of the CMV-V. marina isolate with a stock polyclonal antiserum against the CMV-cucumber isolate (4) were observed in sodium dodecyl sulfate-immunodiffusion. To determine the specific CMV subgroup, total RNA was extracted from inoculated leaves of C. quinoa using the Total Plant RNA Extraction Miniprep System (Viogene, Sunnyvale, CA). A DNA fragment of 940 bp covering the 3' end of the coat protein gene and C-terminal noncoding region of RNA-3 was amplified using the Cucumovirus-specific primers (3) after reverse transcription (RT)-PCR with AccuPower RT/PCR PreMix Kit (Bioneer, Daejeon, Korea). The product was gel purified by Micro-Elute DNA/Clean Extraction Kit (GeneMark Technology Co., Tainan, Taiwan) and cloned in yT&A Cloning Vector System (Yeastern Biotech Co., Taipei, Taiwan) for sequencing (Mission Biotech Co., Taipei, Taiwan) and the sequence was submitted to GenBank (No. HM015286). Pairwise comparisons of the sequence of CMV-V. marina isolate with corresponding sequences of other CMV isolates revealed the maximum (95 to 96%) nucleotide identities with CMV subgroup IB isolates (strains Nt9 and Tfn) compared with 94 to 95% identities with subgroup IA isolates (strains Y and Fny) or 77 to 78% identities with subgroup II (strains LS and Q). These results suggest that CMV is the causal agent for the mosaic disease of V. marina in Taiwan and the isolate belongs to subgroup I. To our knowledge, this is the first report of V. marina as a natural host of CMV. This strain of CMV with specific pathogenicity could threaten crop production in the coastal zones. In addition, V. marina associated with native coastal vegetation was injured by CMV infection, which might lead to ecological impacts on shoreline fading. References: (1) A. A. Brunt. Surveys for Plant Viruses and Virus Diseases in Solomon Islands. FAO, Rome, 1987. (2) C. Büchen-Osmond, ed. Viruses of Plants in Australia. Retrieved from http://www.ictvdb.rothamsted.ac.uk/Aussi/aussi.htm . September, 2002. (3) S. K. Choi et al. J. Virol. Methods 83:67, 1999. (4) S. H. Hseu et al. Plant Prot. Bull. (Taiwan) 29:233, 1987.

Successful treatment of refractory septic arthritis caused by salmonella and staphylococcus aureus with preservation of graft function in a long-term renal transplant recipient by total withdrawal of immunosuppressants.

An 18-year-old female had received a 2 HLA incompatible renal transplant 10 years before. She initially presented with septic arthritis and osteomyelitis caused by Salmonella enterica co-infected with Staphylococcus aureus of her left knee with development of secondary septic arthritis of the right knee and left shoulder. This was complicated by a recurrent subcutaneous abscess and intermittent high fever. The infection was successfully treated with a combination of a prolonged course of antibiotics, twice joint washout and debridement, repeat aspiration, hyperbaric oxygen therapy and a total withdrawal of immunosuppressant resulting in good joint function and preservation of normal renal graft function. In our experience, it was possible to keep stable renal graft function in spite of complete withdrawal of immunosuppressants for 12 months in a recipient with 2 HLA mismatches.

Outcome and risk factors for mortality in children with acute renal failure.

BACKGROUND: Acute renal failure (ARF) is an important cause of morbidity and mortality in children. Here, we investigate etiology, comorbidities, outcome and risk factors associated with mortality in these children with ARF. METHODS: We retrospectively reviewed the characteristics of 58 children with ARF diagnosed between January 1997 and December 2006 at a single institute. Factors including age, sex, clinical features and laboratory parameters were compared between survivors and non-survivors. RESULTS: ARF was secondary to extrarenal causes in 79.3% of cases. Sepsis (18.9%), hematooncologic disease (18.9%) and cardiovascular disease (18.9%), were the main causes of ARF. Primary renal disease due to acute glomerulonephritis, nephrotic syndrome, hemolytic uremic syndrome and obstructive uropathy accounted for 20.7% of the cases. The overall mortality rate was 51.7%. There were no significant differences between survivors and non-survivors in gender and changes in the peak levels of calcium, phosphorous and uric acid levels. The mortality rate was significantly higher when ARF occurred in younger children (p = 0.019), secondary to systemic disease (p = 0.038, odds ratio 4.3; 95% confidence interval (CI) 1.0, 17.9), sepsis (p < 0.001, odds ratio 19.7; 95% CI 5.1, 76.4), use of ventilator (p < 0.001, odds ratio 35; 95% CI 6.7, 182.7), multiple organ failure (p < 0.001) and non-use of renal replacement therapy (p = 0.018, odds ratio, 3.6; 95% CI interval 1.2, 10.6) on univariate analysis. Multiple logistic regression analysis revealed that sepsis (p = 0.011, odds ratio, 11.3; 95% CI 1.7, 73.0) and numbers of organ failures (p = 0.001, odds ratio 8.14; 95% CI 2.5, 26.7) were independently associated with mortality. CONCLUSION: This study found that sepsis and number of organ failures were independent predictors of mortality in children with ARF.

Carcinoembryonic antigen in monitoring of response to cetuximab plus FOLFIRI or FOLFOX-4 in patients with metastatic colorectal cancer.

First-line treatment of metastatic colorectal cancer with combinations of cetuximab and irinotecan-based or oxaliplatin-based chemotherapy has shown promising efficacy. The clinical response to such treatment is generally assessed by tumor measurement through imaging. This study was performed to evaluate the correlation between serial changes in imaging results and carcinoembryonic antigen (CEA) levels. In 64 patients with metastatic colorectal cancer receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy we retrospectively analyzed the relationship between changes in serum CEA and changes in imaging results throughout the treatment course. Response in terms of serum CEA change was defined as a >/=50% drop in CEA level for more than 4 weeks. The sensitivity and specificity of serum CEA changes after targeted chemotherapy in relation to imaging results were 80.5% (33/41) and 73.9% (17/23), respectively, with a diagnostic accuracy of 78.1% (50/64). The progression-free survival time of responders assessed by serum CEA change was significantly longer than that of nonresponders (p=0.0091). Our results highlight the importance of serum CEA monitoring in assessing the response to targeted chemotherapy and in predicting the prognosis of patients with metastatic colorectal cancer.

Prognostic significance of pre- and postoperative serum carcinoembryonic antigen levels in patients with colorectal cancer.

BACKGROUND: To evaluate the prognostic significance of pre- and postoperative serum carcinoembryonic antigen(CEA) levels in colorectal cancer (CRC) patients. METHODS: 425 CRC patients underwent curative resection at our institution. Their pre- and postoperative serum CEA level was classified into two groups according to concentration: normal CEA (<5.0 ng/ml) and abnormal CEA (> or =5.0 ng/ml). RESULTS: Of all patients, abnormal pre- and postoperative serum CEA levels were observed in 181 (42.6%) and 48 (11.3%) patients, respectively. Abnormal preoperative serum CEA level was significantly correlated with the tumor located in the colon, the depth of tumor invasion, the status of lymph node metastasis, UICC stage, and the presence of postoperative relapse (p < 0.05). Concurrently, an abnormal postoperative serum CEA level was also prominently related to the above corresponding parameters (p < 0.05), except for the tumor location. Patients with a failed conversion of abnormal preoperative value to normal postoperative concentration were found to have the worst overall survival rate. Abnormal pre- and postoperative serum CEA levels were single independent predictors for survival and postoperative relapse, respectively. CONCLUSIONS: The identification of abnormal pre- and postoperative serum CEA levels may be useful in the auxiliary cancer prognosis or postoperative surveillance of CRC patients.

ENDO-GIA staplers for side-to-side anastomosis of veins.

OBJECTIVE: To study the application of ENDO-GIA staplers for the side-to-side anastomosis of veins. MATERIALS AND METHODS: An animal study was conducted. Five dogs received side-to-side anastomosis of allograft IVC by ENDO-GIA staplers (Group 1). In addition, five received the same operation with right renal vein reimplantation to allograft IVC (Group 2). Five dogs, receiving the same operation as in Group 1 using polypropylene sutures (control group, Group 3). An autopsy was performed if the dogs survived more than 8 weeks. RESULTS: The IVC anastomosis remained patent in four subjects (80%) for Group 1, in five subjects (100%) for Group 2 and in four subjects (80%) for Group 3. CONCLUSIONS: From the results of our experiment, ENDO-GIA staplers can be considered for use in the side-to-side anastomosis of large veins such as piggyback cavacaval side-to-side anastomosis in cadaveric orthotopic liver transplantation (OLT) or side-to-side splenorenal shunt in portal hypertension.

Imaging cells and tissues with refractive index radiology.

Can individual cells, including live cells, be imaged using hard x rays? Common wisdom until now required sophisticated staining techniques for this task. We show instead that individual cells and cell details can be detected in culture solution and tissues with no staining and no other contrast-enhancing preparation. The sample examined can be much thicker than for many other microscopy techniques without sacrificing the capability to resolve cells. The key factor in our approach is the use of a coherent synchrotron source and of contrast mechanisms based on the refractive index. The first successful tests were conducted on a variety of cell systems including skin and internal leaf cells, mouse neurons, rabbit fibroblast cells, and human tumor cells.

Assembly of a robust, thermally stable porous cobalt(II) nicotinate framework based on a dicobalt carboxylate unit.

A series of robust, thermally stable open-framework cobalt nicotinate compounds, Co(2)(H(2)O)[C(6)H(4)O(2)N](4).0.5CH(3)CH(2)OH.0.5H(2)O (1), Co(2)(H(2)O)[C(6)H(4)O(2)N](4) (2), and Co(2)(H(2)O)[C(6)H(4)O(2)N](4).C(6)H(5)CH(2)OH (3), based on rigid dimetallic carboxylate clusters as the basic building unit have been prepared. Single-crystal X-ray crystallographic analyses of 1 and 3 reveal the host framework possessing an effective channel area with the dimensions of 10.8 x 4.5 A. These channels can accommodate guest molecules of various sizes and shapes such as ethanol, water, and benzyl alcohol. Thermogravimetric analysis shows a two-step weight loss corresponding to the loss of guest molecules followed by the loss of coordinated water. The host framework is thermally stable up to 295 degrees C. The cobalt nicotinate host remains intact, even upon the removal of the guest to form compound 2 as revealed by single-crystal X-ray diffraction analysis. Crystal data for 1: Co(2)(H(2)O)[C(6)H(4)O(2)N)](4).0.5CH(3)CH(2)OH.0.5H(2)O, fw = 656.33, triclinic, space group P(-)1, a = 10.5407(2) A, b = 11.8266(3) A, c = 14.1122(2) A, alpha = 106.878(4) degrees, beta = 102.411(2) degrees, gamma = 111.011(3) degrees, V = 1467.9(5) A(3), Z = 2. Crystal data for 2: Co(2)(H(2)O)[C(6)H(4)O(2)N](4), fw = 624.28, triclinic, space group P(-)1, a = 10.507(3) A, b = 11.824(2) A, c = 14.113(3) A, alpha = 107.06(2) degrees, beta = 102.39(2) degrees, gamma = 111.105(16) degrees, V = 1459.5(6) A(3), Z = 2. Crystal data for 3: Co(2)(H(2)O)[C(6)H(4)O(2)N](4).C(6)H(5)CH(2)OH, fw = 732.42, triclinic, space group P(-)1, a = 10.6671(6) A, b = 12.0063(7) A, c = 14.0658(8) A, alpha = 106.7180(10) degrees, beta = 102.2790(10) degrees, gamma = 111.1900(10) degrees, V = 1504.1(6) A(3), Z = 2. The magnetic exchange coupling between the dicobalt centers for compounds 1 and 3 are analyzed on the basis of both the Curie-Weiss expression and a binuclear magnetic model. The negative values of the magnetic exchange coupling constant indicate the antiferromagnetic nature within the cobalt dimer.

Inhibition of thymidylate synthase activity by antisense oligodeoxynucleotide and possible role in thymineless treatment.

Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer. However, efficacy of TS-targeted anticancer drugs is limited by the development of drug resistance as a result of TS gene amplification. In this work, a phosphorothioated antisense oligonucleotide (ODN), designated ATS-2, was used to suppress cellular synthesis of TS. ATS-2 at 0.2 microM concentration was mixed with lipofectin in a charge ratio of 1:1 and was used to treat the human embryonic kidney (HEK) cell line. A reduction of TS mRNA and protein was achieved. Furthermore, a dose-dependent reduction of cumulative viable cells of up to 98% was observed. Flow cytometer analysis of cell cycle progression indicates that ATS-2-treated cells were arrested and went into apoptosis at the S phase, possibly because of thymidine shortage, suggesting that ATS-2 is specifically effective for dividing cells. When used in combination with the anticancer drug FdUrd, ATS-2 exerted a additive inhibitory effect on cellular proliferation. To elucidate the possible role of cellular thymidine kinase (TdR kinase) in ATS-2 treatment, a second cell line, HeLa, was used. Both HEK and HeLa have similar rates of cell division and ODN uptake. In contrast to HEK, which was shown to have very low levels of TdR kinase activity in [(3)H]thymidine incorporation experiments, [(3)H]thymidine incorporation in HeLa was 15-fold greater than that of HEK. We found that HeLa cells were sensitive to FdUrd but were rather resistant to ATS-2. On the contrary, HEK cells were sensitive to ATS-2 but insensitive to FdUrd. Effects of ATS-2 and FdUrd are, therefore, complementary in thymineless treatment too.