There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

ContextComplications of atherosclerosis cause most morbidity and mortality
in patients with diabetes mellitus. Despite the frequency and severity of
disease, proven medical therapy remains incompletely understood and underused.ObjectiveTo review the epidemiology, pathophysiology, and medical and invasive
treatment of atherosclerosis in patients with diabetes mellitus.Data SourcesUsing the index terms diabetes mellitus, myocardial infarction, peripheral vascular
diseases, cerebrovascular accident, endothelium, vascular smooth muscle, platelets, thrombosis, cholesterol, hypertension, hyperglycemia, insulin, angioplasty, and coronary artery bypass, we
searched the MEDLINE and EMBASE databases from 1976 to 2001. Additional data
sources included bibliographies of identified articles and preliminary data
presented at recent cardiology conferences.Study SelectionWe selected original investigations and reviews of the epidemiology,
pathophysiology, and therapy of atherosclerosis in diabetes. We selected randomized,
double-blind, controlled studies, when available, to support therapeutic recommendations.
Criteria for data inclusion (168 of 396) included publication in a peer-reviewed
journal or presentation at a national cardiovascular society–sponsored
meeting.Data ExtractionData quality was determined by publication in peer-reviewed literature.
Data extraction was performed by one of the authors.Data SynthesisDiabetes mellitus markedly increases the risk of myocardial infarction,
stroke, amputation, and death. The metabolic abnormalities caused by diabetes
induce vascular dysfunction that predisposes this patient population to atherosclerosis.
Blood pressure control, lipid-lowering therapy, angiotensin-converting enzyme
inhibition, and antiplatelet drugs significantly reduce the risk of cardiovascular
events. Although diabetic patients undergo revascularization procedures because
of acute coronary syndromes or critical limb ischemia, the outcomes are less
favorable than in nondiabetic cohorts.ConclusionsSince most patients with diabetes die from complications of atherosclerosis,
they should receive intensive preventive interventions proven to reduce their
cardiovascular risk.

Diabetes and atherosclerosis: epidemiology, pathophysiology, and management.

The biochemistry and medical significance of the flavonoids.

Standing watch over the proteome, molecular chaperones are an ancient and evolutionarily conserved class of proteins that guide the normal folding, intracellular disposition and proteolytic turnover of many of the key regulators of cell growth, differentiation and survival. This essential guardian function is subverted during oncogenesis to allow malignant transformation and to facilitate rapid somatic evolution. Pharmacologically 'bribing' the essential guard duty of the chaperone HSP90 (heat-shock protein of 90 kDa) seems to offer a unique anticancer strategy of considerable promise.

HSP90 and the chaperoning of cancer.

Japan and Thailand have high incidences of bile duct carcinoma and gallstones. The presence of Helicobacter bilis (H. bilis) detected by polymerase chain reaction (PCR) and 16S rRNA analysis in bile samples from Chileans with chronic cholecystitis was reported. The association between H. bilis in bile and biliary tract malignancies has not been investigated, and therefore the aim of this study is to determine whether malignant diseases of the biliary tract are associated with the presence of H. bilis in bile samples obtained from two high-risk populations. Bile samples from 45 Japanese and 40 Thai patients were subjected to PCR analysis using H. bilis-specific primers, and six of the H. bilis amplicons were sequenced. Thirteen out of 15 (87%) Japanese and 11 out of 14 (79%) Thai patients with bile duct or gallbladder cancer tested positive for the presence of H. bilis in their bile. Eight out of 16 (50%) Japanese and 10 out of 26 (38%) Thai patients with gallstone and / or cholecystitis tested positive for H. bilis. Only 4 out of 14 (29%) subjects without biliary disease tested positive for H. bilis among the Japanese. Bile duct and gallbladder cancer showed significantly higher positive rates for H. bilis than did the non-biliary diseases among the Japanese (P < 0.01) and the odds ratios for bile duct or gallbladder cancer with H. bilis in comparison with gallstone and / or cholecystitis were 6.50 (95%CI 1.09 - 38.63) in the Japanese and 5.86 (1.31 - 26.33) in the Thai patients. In conclusion, H. bilis infection in bile was associated with biliary tract and gallbladder cancers in two high risk populations, Japanese and Thai.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.2002.tb01327.x

Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract.

Nestin is a class VI intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.

Nestin in gastrointestinal and other cancers: effects on cells and tumor angiogenesis.

Heat shock proteins (hsps) are thought to play important roles in the cell cycle and various processes of carcinogenesis. Therefore, we evaluated the expression of hsps, mainly hsp90 and hsp70, in human breast cancer tissues. Hsp90alpha mRNA was expressed at much higher levels in the cancerous tissue than in the non-cancerous tissue. In addition, a close correlation between hsp90alpha mRNA expression and the proliferating-cell-nuclear-antigen labeling index (PCNA LI) was observed for the cancerous tissue. These findings suggest that increased expression of the hsp90alpha isoform may play a role in cell proliferation. On the other hand, hsp90beta mRNA expression was significantly higher in poorly differentiated carcinomas than in well differentiated carcinomas of the breast. The intracellular localization of hsp70 was consistent with that of ubiquitin. In specimens showing hsp70 in the nucleus, the PCNA LI was significantly high. Hsc73 mRNA, a member of the hsp70 family, was also expressed at higher levels in cancerous tissues associated with a high PCNA LI than in non-cancerous tissues. These results suggest that hsp90alpha may play a role in cancer cell proliferation and that hsp90beta may contribute to cell differentiation and structural constitution. In addition, hsp70, especially hsc73, is related to ubiquitin and seems to be a marker for cancer proliferation.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.1996.tb02119.x

Expression and roles of heat shock proteins in human breast cancer

CD34 is commonly used as an endothelial cell marker of tumor vessels. However, this marker detects not only newly formed, but also pre-existing large blood vessels. Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells. In this study, whether nestin is a novel angiogenesis marker in colorectal cancer was examined. HCT-15, a human colon cancer cell line, was subcutaneously implanted into the dorsum of nude mice. After the tumor grew, the mice were perfused with fluorescent beads (Fluospheres). Then, the tumor tissues were used for immunofluorescence staining using nestin and the CD34 antibody. Immunohistochemistry was performed with nestin and CD34 on 101 human colorectal cancer tissue samples. Proliferating endothelial cells were detected immunohistochemically by a proliferating cell nuclear antigen (PCNA) antibody. Clinicopathological factors and prognosis were compared between two groups: that with a microvessel density (MVD) higher than the median MVD and that with MVD lower than the median MVD, as detected by nestin and CD34 labellings. Nestin was localized in endothelial cells in small blood vessels (median, 9.06 microm), whereas CD34 was localized in large blood vessels (median, 9.67 microm) in nude mice. The diameter of nestin-positive vessels was smaller than that of CD34-positive vessels in human colorectal cancer. The number ratio of PCNA-positive cells to nestin-positive vascular endothelial cells was higher than that of PCNA-positive to CD34-positive cells (p=0.002). There were no correlations between nestin-positive blood vessels and clinicopathological factors, but the prognosis was worse in the highly nestin-positive MVD group (p=0.071). Nestin is considered a novel angiogenesis marker of proliferating endothelial cells in colorectal cancer tissue.

/pdf/identification-of-neovasculature-using-nestin-in-colorectal-2rp7eybabo.pdf

Identification of neovasculature using nestin in colorectal cancer.

We used Helicobacter pylori sero-positivity and mucosal atrophy as detected by the serum pepsinogen method to identify H. pylori infection-negative gastric cancer patients with or without atrophy. One hundred and six of 748 (14.2%) primary gastric cancer patients were infection-negative by a serum antibody detection system. Further, 121 (16.2%) of the 748 were negative for gastric mucosal atrophy by the pepsinogen method, of whom 15/748 (2.0%) were H. pylori-negative by pepsinogen I level (>70 ng/mL) and pepsinogen I/II ratio (>3.0). Twenty-seven of 782 (3.6%) gastric cancer patients were H. pylori-negative by antibodies and severe atrophy as determined by pepsinogen I level (<30 ng/mL) and pepsinogen I/II ratio (<2.0). H. pylori-negative gastric cancer patients with severe atrophy likely had a previous infection. These results indicate that the actual number of H. pylori-negative patients is 2.0% at minimum and 10.6% (14.2% minus 3.6%) at maximum in the general Japanese population. Five of 15 (33%) cases displaying neither anti-H. pylori antibodies nor atrophy were intestinal-type and 10 (67%) were diffuse-type adenocarcinomas. Thirteen surgical patients with primary gastric cancer displaying neither antibodies nor mucosal atrophy were further analyzed for pathological and phenotypic characteristics. The mucin phenotype was divided into four gastric, five gastric and intestinal, two intestinal and two null types, independent of histological classification. Intestinal phenotype elements were detected by Cdx2 immunohistochemical methods in nine of 13 (70%) cases examined. We conclude that a small fraction of gastric cancer patients displayed multifactorial carcinogenesis without H. pylori infection, indicating that gastric cancer risk still exists in the absence of H. pylori infection, at an incidence of 2.0% at minimum and 10.6% at maximum in the general Japanese population.

Zenya Naito

Papers

Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract.

Nestin in gastrointestinal and other cancers: effects on cells and tumor angiogenesis.

Expression and roles of heat shock proteins in human breast cancer

Identification of neovasculature using nestin in colorectal cancer.

Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: Incidence and pathological characteristics