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BACKGROUND: We previously reported that CEA kinetics are a marker of progressive disease (PD) in metastatic colorectal cancer (mCRC). This study was specifically designed to confirm CEA kinetics for predicting PD and to evaluate CA19-9, cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) kinetics. METHODS: Patients starting a chemotherapy (CT) with pre-treatment CEA > 5 ng/mL and/or CA19.9 > 30 UI/mL were prospectively included. Samples were collected from baseline to cycle 4 for CEA and CA19-9 and at baseline and the sixth week for other markers. CEA kinetics were calculated from the first to the third or fourth CT cycle. RESULTS: A total of 192 mCRC patients were included. CEA kinetics based on the previously identified >0.05 threshold was significantly associated with PD (p

Vitamin D is widely known to regulate bone health, but there is increasing evidence that it may also ameliorate colitis through inflammation, cell proliferation and apoptosis, and the microbiota. The purpose of this review is to systematically examine the mechanisms by which vitamin D reduces colitis. PubMed and Web of Science were searched for articles published between 2008 and 2019 using key words such as “vitamin D,” “colitis,” “inflammatory bowel disease,” “inflammation,” “apoptosis,” “cell proliferation,” and “gut bacteria”. Retrieved articles were further narrowed and it was determined whether their title and abstracts contained terminology pertaining to vitamin D in relation to colitis in human clinical trials, animal studies, and cell culture/biopsy studies, as well as selecting the best match sorting option in relation to the research question. In total, 30 studies met the established criteria. Studies consistently reported results showing that vitamin D supplementation can downregulate inflammatory pathways of COX-2, TNF-α, NF-κB, and MAPK, modify cell kinetics, and alter gut microbiome, all of which contribute to an improved state of colitis. Although vitamin D and vitamin D analogs have demonstrated positive effects against colitis, more randomized, controlled human clinical trials are needed to determine the value of vitamin D as a therapeutic agent in the treatment of colitis.

Electrochemical metallization (ECM) cell kinetics are strongly determined by the electrolyte and can hardly be altered after the cell has been fabricated. Solid-state property tunable electrolytes in response to external stimuli are therefore desirable to introduce additional operational degree of freedom to the ECM cells, enabling novel applications such as multistate memory and reconfigurable computation. In this work, we use Ge2Sb2Te5(GST) as the electrolyte material whose solid state is switched from the amorphous(a) to the crystalline(c) phase thermally. Electrical heating too is readily achievable. The resistive switching characteristics of the cells with different GST phases are examined. The magnitude of the high resistance, the SET voltage and the on/off ratio are found to be considerably affected by the solid phase of GST, whereas the magnitude of the low resistance is least affected. Moreover, a transition from volatile to nonvolatile SET switching is only observed for c-GST based cell under prolonged voltage sweep, but not for a-GST based cell. This work provides a springboard for more studies on the manipulation of the ECM cell kinetics by tunable electrolyte and the resulting unprecedented device functionalities.

Digital holographic cytometry (DHC) permits label-free visualization of adherent cells. Dozens of cellular features can be derived from segmentation of hologram-derived images. However, the accuracy of single cell classification by these features remains limited for most applications, and lack of standardization metrics has hindered independent experimental comparison and validation. Here we identify twenty-six DHC-derived features that provide biologically independent information across a variety of mammalian cell state transitions. When trained on these features, machine-learning algorithms achieve blind single cell classification with up to 95% accuracy. Using classification accuracy to guide platform optimization, we develop methods to standardize holograms for the purpose of kinetic single cell cytometry. Applying our approach to human melanoma cells treated with a panel of cancer therapeutics, we track dynamic changes in cellular behavior and cell state over time. We provide the methods and computational tools for optimizing DHC for kinetic single adherent cell classification.

Drug-induced allergy (DIA), an unexpectedly triggered side effect of drugs used for therapeutic purposes, is a serious clinical issue that needs to be resolved because it interrupts the treatment of the primary disease. Since conventional allergy testing is insufficient to accurately predict the occurrence of DIA or to determine the drugs causing it, the development of diagnostic and predictive tools for allergic reactions is important. We demonstrated a novel method, termed high-sensitive allergy test (HiSAT), for the rapid diagnosis of allergy (within 1 hr; with true-positive diagnosis rates of 89% and 9% for patients with and without allergy-like symptoms, respectively). HiSAT analyzes the cell kinetics as an index against chemotactic factors in a patient’s serum, as different from the diagnosis using conventional methods. Once allergy has occurred, HiSAT can be used to determine the causative medicine using culture supernatants incubated with the subject’s lymphocytes and the test allergen. This test is more efficient (60%) than the lymphocyte transformation test (20%). Furthermore, in HiSAT, cell mobility significantly increases in a dose-dependent manner against supernatant incubated with lymphocytes from a subject with pollinosis collected at a time when the subject is without allergic symptoms and the antigen. The result demonstraed that HiSAT might be a promising method to rapidly diagnose DIA or to determine with high accuracy the antigen causing allergy.

Using tritium-labeled thymidine histoautoradiography, the AgNOR staining technique and Ki67-MIB-1 immunohistochemistry to study cell kinetics, prostate cancer can be subdivided into slowly, moderately and rapidly proliferating tumors. These are important supplementary methods and prerequisites for a grading as low, intermediate and high-grade in addition to classical histology and cytology. Cytometry of DNA can confirm the cell kinetics of prostate cancer by detection of a predominance of diploid or aneuploid cell nuclei but should only be evaluated together with histological investigations. All histology-based analyses of cell kinetics encompass the classical highly and poorly differentiated glandular and cribriform patterns as well as solid undifferentiated structures and the various subcategories. The malignancy grading of prostate cancer can result from the summation of histological grading and cell kinetic analyses, as long as the named investigations are included. The future perspectives of individualized therapy options, including active surveillance in early low-grade and also for high-grade prostate cancer and new antihormonal treatment in advanced disease, may increasingly rely on tissue biomarkers and advanced technologies for whole genome analysis including next generation sequencing.

Background: Reticulocytes are immature red blood cells containing RNA remnants. Their population kinetics has been documented under various in vivo and in vitro conditions, including after storage of red blood cells in blood banks. The purpose of this study was to describe the influence of blood bank storage on the kinetics of reticulocyte disappearance by in vitro culturing. Method: Samples of reticulocyte-enriched fractions (Percoll density-gradient) were obtained over different storage times from six red blood cell units stored in additive solution-1 (AS-1). Reticulocyte fractions were then cultured in enriched media at 37 °C and analyzed by flow cytometry with thiazole orange taking into account hemolysis. Results: Density-gradient enriched reticulocyte fractions were obtain from standard red blood cell units with

The restoration of the skin barrier in acute and chronic wounds is controlled by several molecular mechanisms that synergistically regulate cell kinetics, enzymatic functions, and neurovascular activation. These pathways include genetic and epigenetic activation, which modulate physiological wound healing. Our review describes the genetic background of skin repair, namely transcription-independent diffusible damage signals, individual variability, epigenetic mechanism, controlled qualitative traits, post-translational mechanisms, antioxidants, nutrients, DNA modifications, bacteria activation, mitochondrial activity, and oxidative stress. The DNA background modulating skin restoration could be used to plan new diagnostics and therapeutics.

In this study, we aimed to investigate whether the procedure and product kinetics differ according to age groups in advanced-age MM patients who underwent autologous HSCT. 59 patients who underwent autologous HSCT were retrospectively analyzed. Then, the patients were divided into two groups as 60–65 years and ?65 years. It was significantly lower in ?65 years group (p = 0.008) and proportionally, the procedure duration was also significantly shortened in this group (p = 0.013). Total number of collected CD34 positive stem cells was 6.20 × 106 (±3.83) in 60–65 years group while it was 5.51 × 106 (±2.48) in ?65 years group with no statistically significant difference (p = 0.825). In conclusion, there was no significant difference in terms of the number of collected CD34-positive stem cells in this study that investigates the mobilization data, procedure and product kinetics, we think that successful stem cell mobilization can be performed in appropriately selected patients regardless of age. © 2018 Elsevier Ltd

Aim: Though odontogenic lesions have in common origin from the primitive odontogenic epithelium , there is a diversity in their initiation behavior and growth. The aggressive nature of odontogenic keratocyst similar to ameloblastoma in comparision with the other common odontogenic (dentigerous and radicular) cyst could be due to possible differences in their epithelial linings. PCNA (Proliferating cell nuclear antigen) is a cell cycle related antigen, used in the study of cell kinetics of these epithelial linings, to corelate the biological behaviour among these common odontogenic lesions. Objectives: This paper has intended to study the cell kinetics of 4 selected odontogenic lesions (dentigerous cyst, radicular cyst,odontogenic keratocyst and ameloblastoma) to demonstrate differences in their epithelial linings. Material and Methods: Sixty samples of paraffin embedded tissue specimens (archival tissues) were included (15 radicularcysts, 15 odontogenic keratocysts; 15 dentigerous cysts and15 Ameloblastoma. Results: Among cyst OKC had higher values than DC and RC. When staining results of all the cyst were compared individually with ameloblastoma ,the staining results of OKC was similar to ameloblastoma ,and ameloblastoma presented higher values than OKC (p=0.000). Conclusion: The results of this study show 1) Though OKC and DC are developmental in origin and radicular cyst is inflammatory, OKC has intrinsic growth potential among these cyst 2). Ameloblastoma has similar proliferative potential as OKC and hence it has been reinforced as KCOT(Keratocystic odontogenic tumour) in the recent classification.

Introduction A putative role for progesterone in the growth of meningioma has been suggested. The aim of this study was to attest the role of progesterone receptor (PR) in predicting the biological behavior of meningioma. Material and methods The study included 30 cases of meningioma, 15 (50%) recurrent and 15 (50%) non-recurrent. The immunohistochemical expression of PR was studied. Cell kinetic using the Ki67/MIB-1 labelling index (LI) was evaluated and correlated to PR expression. Results PR expression was significantly more common in benign meningioma (BM) than atypical meningioma (AM) and malignant meningioma (MM). The mean Ki-67/MIB-1 LI was significantly highest in MM, high in AM and lowest in BM. In PR-negative meningioma, the mean Ki-67/MIB-1 LI was significantly higher compared with PR-positive meningioma. In the recurrent group, PR was frequently immunonegative and the mean Ki-67/MIB-1 LI was higher than that in the non-recurrent group. The difference in PR expression between non-recurrent and recurrent cases was significant only in BM. The difference in Ki-67/ MIB-1 LI was significant only when recurrent meningioma was compared with non-recurrent tumor, irrespective of the grade. Conclusion BM expresses PR more than AM and MM. The absence of this expression in BM implies a likely risk for recurrence. Ki-67/MIB-1 LI is valuable to predict tumor grade and the overall risk of recurrence. However, it must be interpreted with caution in BM.

Central venous access is often used during apheresis procedure in stem cell collection. The aim of the present study was to evaluate whether central or peripheral venous access has an effect on stem cell yield and the kinetics of the procedure and the product in patients undergoing ASCT after high dose therapy. A total of 327 patients were retrospectively reviewed. The use of peripheral venous access for stem cell yield was significantly more frequent in males compared to females (p = 0.005). Total volume of the product was significantly lower in central venous access group (p = 0.046). As being a less invasive procedure, peripheral venous access can be used for stem cell yield in eligible selected patients. © 2016 Elsevier Ltd.

For evaluation of the efficiency estimation of compensation of anemia by means of the appearing additional cell’s flaw into peripheral blood the method of has been used.

Background and aims Aberrant crypt foci (ACF) are preneoplastic lesions in animal models of colorectal cancer. The aim of the study is to investigate if ACF are involved in human colorectal carcinogenic process and if they can be helpful in predicting the presence of a colorectal neoplasia. Methods The study included, between 2003 and 2005, 182 patients, 62 with adenoma, 55 with colorectal carcinoma, 53 without colorectal lesions, and 12 with nonneoplastic mucosal polyps. The number of rectal ACF was determined by colonoscopy. Proliferation and apoptosis indexes were evaluated by immunohistochemistry in rectal ACF, in normal rectal mucosa, and in carcinomatous tissue. Results The mean number of rectal ACF in patients with rectal neoplasia was 12.64, significantly higher than in patients with neoplastic lesions elsewhere in the colon (p?=?0.01). The apoptosis index in ACF of patients with colorectal carcinoma or adenoma aged 50 years or older was significantly lower than in younger patients (1.3% vs 2.7%, p?=?0.01) and, in patients with carcinoma, lower than in normal mucosa (1.1% vs 2.1%, p?=?0.002). The proliferation index was significantly higher in ACF of patients with colorectal neoplasia aged less than 50 years than in normal mucosa (10.9% vs 7.7%, p?=?0.02). The apoptosis index in ACF foci of patients with carcinoma (1.1%) was significantly lower than in patients without lesions (2.2%) and than in normal mucosa (2%). The mean number of ACF is significantly higher in patients with polyps larger than 1 cm (11.28 vs 6.27, p?=?0.02). Conclusion Aberrant crypt foci probably precede the appearance of neoplasia and may be helpful in predicting the presence of a colorectal neoplastic lesion.

The kinetics of cells, keratin, and lipids in the skin could provide useful information about skin biology in health and disease. The kinetics of skin cell turnover are of interest for a variety of physiologic and pathologic conditions. There are also uncertainties regarding the extent of keratinocyte turnover in various skin diseases. Hyperproliferatiation may represent a risk factor for skin cancer and occurs in physiologic conditions such as wound healing.

The chemotherapy of gastrointestinal malignancies remain mostly investigational, although several adjuvant protocols in colorectal cancer and anal cancer are beginning to be accepted as standards against which newer regimens are to be compared. Chemotherapy regimens are best understood and appreciated with a basic understanding of cancer biology, tumour cell kinetics, and drug toxicities. An appreciation of chemotherapy-induced toxicity and an awareness of their management will help the gastroenterologist be an active participant in the multidisciplinary team caring for the patient with gastrointestinal malignancies.

For evaluation of potential staying duration of cells in peripheral blood on the character of cell kinetics, method of mathemati-cal modeling was used. Potential staying duration of cells in peripheral blood was numerically shown to deeply influence on anemia, but only for the small share of cells' death.

Malignant melanoma has been extensively studied concerning methods of predicting progression and clinical outcome. The maximum tumor thickness as measured by Breslow's method is the cornerstone prognostic criterion, but despite this, evolution of the disease in some patients remains unpredictable, confirming that new reliable prognostic factors are awaited. Cell kinetic evaluation has been shown to be a useful tool for assessing the prognosis of breast and gastrointestinal cancer patients. Indeed, in these fields, the mitotic index and MIB-1 expression index, which are indirect estimates of the growth fraction of tumor cell population, are commonly shown to correlate with tumor grade and patient survival and presented as prognostic factors. In melanoma, results of cell kinetic investigations are conflicting: some studies have established a link between high proliferative activity and a bad prognosis, whereas other reports suggest the opposite. The aim of this review is to discuss these findings.

Summary A very rare case of epithelioid hemangioendothelioma (EH) in the tongue is reported. The immunohistochemical studies for Factor VIII, proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were performed. The tumour cell kinetics in EH was evaluated by PCNA immunohistochemistry. PCNA labeling index in the tumour was 57.0%. Furthermore, strong immunohistochemical expression of VEGF was recognized in the cytoplasm of tumour cells. The intense expression of VEGF in EH may indicate its aggressive proliferative activity and metastatic behavior.

Summary. We report cell kinetics, yields and donation experiences of 20 demographically matched allogeneic peripheral blood stem cell (PBSC) donors who were prospectively assigned to undergo either a single 25 l or two consecutive daily 15 l (15 l × 2) apheresis procedures. Procedures were performed using prophylactic intravenous calcium administration after standard granulocyte colony-stimulating factor (GCSF) mobilization (10 μg/kg/d). Central line placements (two each), initial CD34 cell counts (0·077 vs 0·078 × 109/l) and yields (7·9 vs 8·1 × 108 CD34 cells) were similar in the two groups; however, 25 l donors spent significantly less time both in the clinic (7·5 vs 10·8 h) and with central venous catheters in place (8·5 vs 29·5 h) than 15 l × 2 donors. End-procedure platelet counts were below 100 × 109/l in one out of 10 25 l donors versus five out of 10 in 15 l × 2 donors (41%vs 53% mean decrease in platelet counts, P = 0·02). PBSC collection efficiency increased by 37% after 15 l of the 25-l volume had been processed, compared with no significant change during 15 l × 2 procedures. Results similar to these prospective findings were also observed in CD34 yields, symptoms and platelet counts in additional 25 l and 15 l procedures performed during the same period and evaluated retrospectively. This study indicates that a single 25-l apheresis procedure results in similar yields and symptoms, but less donor thrombocytopenia and inconvenience than two consecutive daily 15-l procedures.

Serial colonoscopic observations were prospectively conducted to elucidate the natural history of nonpolypoid tumors. Furthermore, to clarify whether cell kinetic status affects the tumor development, proliferative indices, apoptotic indices, and K-ras codon 12 point mutations on biopsy specimens were investigated.Seventy-five colorectal tumors, 13 polypoid and 62 nonpolypoid type (56 flat elevated and six depressed type) were studied. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method, respectively. Point mutations at K-ras codon 12 were examined by enriched polymerase chain reaction-based restriction fragment length polymorphism assay.The average follow-up period was 22 months (range 1-50). The lesions of subsequent exophytic growth, unchanged shape, depressed growth, and disappearance were observed in 0%, 92%, 0%, and 8% of polypoid type, in 39%, 39%, 13%, and 9% of flat elevated type, and in 33%, 67%, 0%, and 0% of depressed type, respectively. There was no significant difference in tumor size between initial and follow-up colonoscopy. Nonpolypoid tumors apparently changed to the exophytic growth during 2 yr or more. The tumors with exophytic growth had significantly higher proliferative indices/apoptotic indices ratios than those with unchanged morphology and disappearance/depressed growth (p0.05, respectively). K-ras codon 12 point mutations did not correlate with tumor development.Cell kinetic status plays an important role in determining minute colorectal tumor development, but not K-ras codon 12 mutations. Minute nonpolypoid adenomas frequently tend to grow slowly, and nearly 40% of those become the exophytic growth with time. Most of minute nonpolypoid tumors seem to follow the adenoma-carcinoma sequence.

The biological basis for altered fractionation radiotherapy is reviewed in this study. The clinical application of hyperfractionation is based on evidence that late-responding normal tissues are spared more radiation damage than early-responding tissues or tumors when the dose per fraction is decreased to less than 2 Gy. Evidence has also accumulated to indicate that prolonged treatment is detrimental to control tumors due to accelerated repopulation of surviving tumor cells, which is the basis for accelerated fractionation. Recent clinical trials on altered fractionation schedules are also discussed.

BACKGROUND: Mobilization and homing of PBPCs are still poorly understood. Thus, a sufficient algorithm for the prediction of PBPC yield in apheresis procedures does not yet exist. STUDY DESIGN AND METHODS: The decline of CD34+ cells in the peripheral blood during apheresis and their simultaneous increase in the collection bag were determined in a prospective study of 18 consecutive apheresis procedures. A cell-kinetic, four-compartment model describing these changes was developed. Retrospective data from 136 apheresis procedures served to further improve this model. A predictive algorithm for the yield was developed that considered the sex, weight, and height of the patient, the number of CD34+ cells in peripheral blood before apheresis, the inlet flow, and the duration of the apheresis. The accuracy of this algorithm was evaluated by comparison of the predicted and the observed yields of CD34+ cells in 105 prospective autologous and 148 retrospective allogeneic apheresis procedures. RESULTS: The correlation between predicted and observed yields was good for the autologous and allogeneic groups with a correlation coefficient (r) of 0.8979 and 0.8311 (p

WOS: 000089054600005, PubMed ID: 10972859, Cell kinetic information is an important adjuvant to histological grading in some malignant tumors. In the current study, 20 endometrial adenocarcinomas were graded according to the 1988 International Federation of Gynecology and Obstetrics (FIGO) and nuclear grading system and the expression of silver-stained nucleolar organizer regions (AgNOR) and S100-positive Langerhans cells were determined. According to the FIGO grade, eight patients were in grade 1, seven were in grade 2 and five were in grade 3. Nuclear grade 1, 2 and 3 was determined in six, eight and six cases, respectively. Although an overlap was seen in some grade 2 and 3 cases, AgNOR counts were the highest in grade 3. S100-positive Langerhans cells were depleted when the grades elevated. It is concluded that AgNOR and Langerhans cells can be correlated with grades. Further studies, including survival data of the patients, could be performed and AgNOR and Langerhans cells can be correlated with prognosis.

The radiolabelling of blood cellular elements with PET radionuclides offers a higher sensitivity and resolution than conventional imaging, but short-lived PET radionuclides have limited clinical use in cell labelling. Medium half-life PET radionuclides, such as 55 Co (t 1 /2 = 18.2 h), 52 Fe (t 1 /2 = 8.3 h) and 66 Ga (t 1 /2 = 9.4 h), enable quantitative uptake and cell kinetic studies with radiolabelled blood cellular elements. Co(II) oxine, Co(III) tropolonate, Fe(III) oxine, Ga(III) oxine and Ga(III) MPO were prepared using gamma-emitting radionuclides and a number of cell labelling parameters were investigated. The uptake of 57 Co(II) oxine into erythrocytes was only 37%, and 65% of the activity eluted from the cells in cell-free plasma within 30 min. In contrast, high leukocyte and erythrocyte labelling efficiencies (> 90%) were obtained with 57 Co(III) tropolonate containing cobalt carrier and the elution in cell-free plasma over 4 h was < 8%. High labelling efficiencies were also observed with 59 Fe(III) oxine and 67 Ga-MPO and the elution from leukocytes over 4 h was < 25%. We conclude that Co(III) tropolonate, Fe(III) oxine and Ga-MPO may be useful for radiolabelling leukocytes for PET investigations.

Malignant tumors differ from healthy tissue, among other things, in their cell kinetics and in a changed energy metabolism. Therefore the objective of this study is to find an answer to the question, whether these cell-biological differences result in a changed thermal output. For this purpose biopsies were taken from human colorectal carcinomas (n=10), on the occasion of colonoscopic examinations; the former were placed into a microcalorimeter, and the occurring thermal flow rates were measured. The results were then compared with corresponding data of biopsies taken from normal colorectal mucosa (n=16) and with data of biopsies taken from colorectal adenomatous tissue (n=18), which can be looked upon as a precancerosis. While tissue from adenocarcinomas showed a significantly higher (t=0/1 h: p

Oxine, tropolonate, and mercaptopyridine-N-oxide (MPO) have been widely used with 111In for platelet labeling. The use of positron emission tomography (PET) radioisotopes for platelet labeling would offer a higher sensitivity and resolution over conventional imaging. The medium half-life PET radioisotope 55Co (t1/2 = 18.2 hours) would enable quantitative uptake and cell kinetic studies with radiolabeled platelets. To identify the optimal complex for radiolabeling of platelets with 55Co, we investigated the platelet uptake of 57Co-oxine, 57Co-tropolonate, and 57Co-MPO in varying different parameters. The platelet uptake of Co-complexes was generally low (5-12%), dependent on time and temperature of incubation and density of platelets but independent of the amount of radioactivity. These findings are not promising for potential PET application.

PURPOSE The present study was to investigate, using cell kinetic methods, whether previous excimer laser treatment affected healing of later corneal epithelial erosions. METHODS The right eyes of rats underwent central excimer corneal stromal-epithelial ablations (ArF 193 nm, 228 pulses, diameter 3,5 mm, 17,3 mJ per pulse, depth about one third of corneal thickness) and were allowed to heal for 15 weeks. Then central circular epithelial abrasions (diameter 3 mm), using N-Heptanol and mechanical debridement, were made on both corneas. The rats were killed 1,2,4 and 6 days after the last treatment. The central stromal thickness, the epithelial cell density, the labelling index (LI) and the mitotic rate (MR) of the peripheral, the midperipheral and the central areas of the corneal epithelium were calculated for each timepoint. RESULTS The central stromal thickness increased equally in the two groups the first day after making the erosion, normalising in both groups during the following days. The corneal epithelium was restored at the same rate in both groups. The cell number per microscopic visual field, the LI and the MR were very similar for the two groups at all timepoints. CONCLUSION Previous excimer laser treatment does not seem to interfere with healing of later epithelial erosions, when studied with cell kinetic methods.

Cell kinetic parameters were measured in four cases of meningioma showing regrowth. The cell cycle time (Tc) and tumor doubling time (Td) were established by histological evaluation of the biopsy specimens and calculation of the growth curve based on computed tomography (CT)/magnetic resonance (MR) images. MIB-1 mouse monoclonal antibody, which recognizes an epitope of the Ki-67 antigen, was used to establish the MIB-1 staining index (SI) (MIB-1-positive nuclei⁄5000 tumor cells) for each tumor. The changes in tumor volume were calculated from CT/MR images, and the Td was estimated from the growth curve. The Tc was calculated using Steel''s formula from the MIB-1 SI and tumor volume. MIB-1 SI varied from 0.0055 to 0.0468, Td from 270 to 1429 days, and Tc from 10.4 to 15.9 days. Furthermore, the potential doubling time (Tp) was calculated using the corresponding Tc and MIB-1 SI (growth fraction) for the four cases; these values varied from 197 to 1645 days and were very close to the Td values. This method of evaluation of tumor Tc and calculation of Tp may be useful for predicting the postoperative course in meningiomas.

Resumo O autor reve o valor da histopatologia e da cinetica das celulas tumorais no prognostico dos tumores gliais. Aspectos microscopicos como sejam a infiltracao dos tecidos vizinhos ou para la dos confins do tumor e a constatado de multifocalidade tumoral sao factores importantes na recorrencia dos gliomas objecto de recessoes macroscopicas totais. As classificacoes histopatologicas destes tumores associadas a tentativa de correlac,ao clinica sao revistas criticamente. E realcada a importância da biopsia estereotaxica no diagnostico histologico e na opcao terapeutica dos gliomas. Os metodos de avaliacao pratica da capacidade proliferativa das celulas tumorais sao a determinacao dos indices proliferativos do PCNA, Ki-67 e MIB1, que se correlacionam com o comportamento biologico dos gliomas.

British radiobiologists have often been at the forefront in taking clinical questions into the laboratory and in taking the results back into the clinic, i.e., what is nowadays labeled as Translational Research. They have published widely and have been very active in lectures, workshops, and discussions, forming an important component of the international communication web, both within the basic science aspects and in the translation from science to medicine, and back again. Major contributions have been made at the cellular and subcellular level, and at the level of multicellular structures, both normal and malignant. The common features of the response of cells to single doses in well-defined conditions have been used to interpret the much greater complexity of tissue and tumor responses treated with repeated small doses in a fractionated course, both of photons and other radiations, with and without chemical modifiers. The many contributions to the field of cell kinetics have provided the tools with which an understanding has been gained of the latency and evolution of radiation damage in different tissues. The prolonged interest in microenvironmental gradients and compensatory responses to injury have provided a framework for designing better radiotherapy schedules, and considerable spin-off to other branches of cancer therapy.

To understand better the repopulation kinetics of tumor cells after radiotherapy, we Investigated changes in cell proliferative parameters after single‐dose irradiation of SCCVII tumors in C3H/He mice and EMT6 tumors in Balb/c mice. The following parameters were determined 0–15 days after single irradiation at 20 or 30 Gy; dividing fraction (DP), potential doubling time (Tpot), number of clonogenic cells per tumor (Ncln), and volume doubling time (Tvol). DF and Tpot were determined by in vivo‐in vitro cytokinesis‐block assay with cytochalasin B, Ncln was measured by in vivo‐in vitro colony‐forming assay, and Tvol was determined by growth delay assay. In both tumors, longer Tpot and lower DF and Ncln were obtained for 3–4 days after irradiation, but in SCCVII tumors these values returned to the pretreatment levels 9 days after irradiation. In EMT6 tumors, Tpot, DF, and Ncln did not return to the pretreatment levels even 12 days after irradiation. In the regrowth phase of both tumors following irradiation at 20 Gy, Tvol was longer than the pretreatment level, although Tpot was similar in SCCVII and only slightly longer in EMT6. Therefore, the cell loss factor in the regrowth phase was considered to be higher than the pretreatment level in both tumors. From the results, recruitment of previously quiescent cells into the proliferative pool in these tumors was suggested to contribute to repopulation after radiation.

Macrophages and α-smooth muscle actin immunopositive myofibroblasts are thought to be crucial cells in granuloma formation. In this study, the reactive cell kinetics was investigated in Sephadex bead-induced rat pulmonary granulomas (1mg/ml saline/head; intravenously) from l hour to 90 days after the injection. Intravenously administered Sephadex beads occluded pulmonary arteries and caused granulomatous pulmonary arteritis. The inflammatory cells appeared first around the trapped beads and then granuloma lesions developed within 24 hours. Three days later, the granulomas mainly consisted of neutrophils, macrophages, eosinophils, and giant cells. Immunohistochemically, the number of ED1-positive macrophages quickly increased 24 hours after the injection, and a large number of macrophages were still found 3 days after the injection. Alpha-smooth muscle actin immunopositive myofibroblasts increased in numbers from 3 to 7 days after theinjection. These results indicate that the appearance of myofibroblasts in pulmonary granulomas might be mediated by macro-phages, which were the most predominant inflammatory cells in the present pulmonary granuloma.

In this paper, overcharging effects of Li-ion polymer cells were investigated and classified with respect to vehicle safety concerns. An advanced cell model is proposed providing better State of Health (SoH) determination for overcharge behavior in operation of Li-ion Polymer batteries. Li-ion polymer cell kinetic parameters were obtained using Electrochemical Impedance Spectroscopy (EIS) method and changes in these parameters were analyzed theoretically in cases of forced charging. Cell equivalent circuit was improved and additional parameters detected according to overcharge states. This yields a better detection and diagnosis capability for Battery Management System (BMS). These equivalent circuits and experimental results provide better classification when defining the irreversible changes caused by overcharging.

✓ The author reviews the molecular genetics, pathology, and cell kinetics of meningiomas and the role that regional multiplicity in the dura mater may play in their recurrence. Malignant and radiation-induced meningiomas are discussed, with summaries of series of 60 patients with frankly malignant lesions treated over a period of 22 years at the University of California, San Francisco, and of 10 patients with meningiomas induced by high-dose radiation therapy. Reviewing a 23-year series of 140 patients with subtotally removed meningiomas who were treated postoperatively with radiation, the author recommends that, with meticulous technique, irradiation is effective in preventing the regrowth of subtotally removed benign meningiomas and of all malignant meningiomas. Adoption of both the microscopical cytological grading system proposed by Jääskeläinen's group in Helsinki and the classification of operations proposed by Donald Simpson is also recommended. Wide removal of dura adjacent to meningioma reduces the risk of recurrence, and determination of the bromodeoxyuridine labeling index provides a valid basis for planning treatment and follow-up evaluations. Increased awareness is necessary for early recognition of radiation-induced meningiomas in patients at risk for developing such tumors. For meningiomas in such sites as the parasellar region and the posterior fossa, conservative removal of tumor followed by irradiation is advocated in preference to a radical operation that may cause neurological injury without being curative.

Forty-three squamous cell carcinomas of the head and neck region were in vivo labelled with the thymidine analogue iododeoxyuridine. Combined flow cytometric (FCM) and immunohistochemical (IHC) analysis was performed, and the following parameters calculated: labelling index (LI), S-phase time (TS) and potential tumor doubling time (Tpot). Complete FCM and IHC analyses could successfully be performed in 31 cases, showing a median LI of 13.6% with FCM and 9.1% with IHC. A correlation achieved between LI/FCM and LI/IHC was due to the aneuploid cases, whereas the diploid cases showed no such correlation. Data indicated that Tpot calculated with LI from IHC (Tpot/IHC) might be a prognostic factor, in contrast to Tpot determined using LI/FCM.

Colorectal cancer is the second leading cause of cancer-related death in America. Historically, chemotherapeutic treatment of colorectal cancer has met with mixed success. Continued research is securing a role for chemotherapy in the treatment of colorectal cancer, with fluoropyrimidines (5-fluorouracil and fluorodeoxyuridine), alone or in combination with modulating agents, being the most promising area of treatment. Knowledge of cell kinetics forms the basis for understanding chemotherapeutic activity and the management of drug-induced side effects. Nursing care is essential to the management of such common side effects as myelosuppression, stomatitis, nausea and vomiting, diarrhea, and cutaneous problems. Inadequate management of side effects can result in serious and distressing complications, including inability to complete therapy, risking an opportunity for potential cure or causing needless suffering and expense. In addition to supporting continued medical research, nurses need to pursue research that identifies the most effective nursing interventions for management of side effects from chemotherapy.

Background Peritoneal fibrosis is an essential precursor condition to the development of encapsulating peritoneal sclerosis (EPS). This serious complication leads to a high mortality rate in peritoneal dialysis (PD) patients. Although several factors, including highly concentrated glucose in the dialysis solution, are believed to be potent agents for peritoneal fibrosis, the underlying mechanism remains unclear. During PD, the dialysis solution continuously generates fluid flow stress to the peritoneum under peristalsis and body motion. Fluid flow stress has been implicated as playing a critical role in the physiologic responses of many cell types. We therefore hypothesized that fluid flow stress may be involved in the pathogenesis of peritoneal fibrosis leading to EPS. Methods To generate fluid flow stress, culture containers were placed on a rotatory shaker in a thermostatic chamber. In this system, the shaker rotated at a speed of 25 rpm with a radius of 1.5 cm. Mesothelial cells were cultured in low-glucose (1000 mg/L) or high-glucose (4500 mg/L) complete medium with and without flow stress. Results Fluid flow stress promoted hyperplasia and epithelial–mesenchymal transition (EMT) of mesothelial cells independent of glucose concentration. Fluid flow stress inhibited expression of ERK (extracellular signal–regulated kinase) and p38 MAPK (mitogen-activated protein kinase) in mesothelial cells. Administration of ERK and p38 MAPK inhibitors replicated the stress-induced morphology of mesothelial cells. Conclusions The present data indicate that fluid flow stress promotes hyperplasia and EMT of mesothelial cells via the MAPK axis, suggesting that fluid flow stress may be involved in the pathogenesis of peritoneal fibrosis.

Purpose: A new flow cytometric technique that allows for two incorporated thymidine analogues to be measured simultaneously and independently has been used to improve the accuracy of in vivo cell kinetic estimates, i.e., the length of S -phase (TS) and potential doubling time ( T pot ). Methods and Materials: The analogues chlorodeoxyuridine and iododeoxyuridine were injected at different times into mice bearing the mouse mammary tumor MCaK. At different times after labeling, the tumors were harvested and prepared for three color flow cytometric analysis of DNA, chlorodeoxyuridine, and iododeoxyuridine. Control experiments showed that similar estimates of T pot were obtained from each label when administered singly, or as staggered pulses. Comparisons were made between T s and T pot calculated from a single label (single point), from the averaged result of the two labels from the same tumor (two point-ave), and from the simultaneous nonlinear fitting of the measured parameters from the two labels, from the same tumor (two point-fit). These estimates of T s and T pot were then compared to reference values obtained by fitting the pooled measured parameters from all the tumors, that were labeled for different periods of time. Results: While all of the methods resulted in similar mean estimates of T s and T pot that were close to the reference values, the fewest assumptions, and the least variability in the results, were obtained using the two point-fit data. Conclusion: The estimation of T pot using two thymidine analogues is more accurate than that obtained from a single label.

Brachytherapy continues to play an important role in the management of cancers of several sites, including the head and neck, brain, uterine cervix, endometrium, and prostate. The physical advantages of brachytherapy result from a superior localization of dose to the tumor volume. In brachytherapy, as radiation is continuously delivered over a period of time, repair of sublethal and potentially lethal damage, proliferation, and other cell kinetic effects modify the response of tumor and normal tissues, resulting in complex dose rate effects that also influence the therapeutic ratio for brachytherapy. There are two different forms of brachytherapy: intracavitary irradiation using radioactive sources that are placed in body cavities in close proximity to the tumor, and interstitial brachytherapy using radioactive seeds implanted directly into tumor volume. Intracavitary radiation is always temporary and usually takes about 1 to 4 days. On the other hand, interstitial brachytherapy can be temporary or permanent. Radioactive sources emitting higher energy photons have better tissue penetration but are more difficult to shield for radiation protection purposes than sources emitting lower energy photons. Longer-lived radioactive sources can be used several times in different patients, which reduces their effective cost compared with shorter-lived radioisotopes. However, for permanent implants, shorter-lived radionuclides can provide higher initial dose rate, which may have biological advantages in some cases. These characteristics of various forms of brachytherapy dictate the choice of radioactive sources for a specific treatment. Recently, a number of new radionuclide sources have been developed, making a wide variety of half-lives and photon energies available to the brachy-therapy community. Conventional sources for brachy-therapy in the United States are cesium 137, iridium 192, iodine 125, and gold 198. The physical characteristics of these sources and of the newly developed sources, americium 241, palladium 103, samarium 145, and ytterbium 169, are described.

Histological, cytological and growth characteristics of prostate carcinoma are presented in this review, as well as the importance of various cell kinetic methods such as autoradiography, DNA- and AgNOR-analysis. By combining these methods with nucleolar grading, carcinoma of the prostate can be divided into two different groups of malignancy regarding therapy and prognosis: I. Carcinoma patients with well differentiated carcinomas and low risk. II. Carcinoma patients with poorly differentiated carcinomas and high risk. Cytogenetic and oncogenetic findings are discussed according to these groups. Special features of neuroendocrinically differentiated carcinomas are also presented. This review contains our own data in addition to information from the literature, and it describes future directions in the research of prostate carcinoma. Prostatic carcinoma is at present the second most common tumor in males. This has led to extensive research and numerous clinical studies on the prostate gland in the recent years.

The purpose of this article is to review the potential advantages of measuring cell kinetic parameters, to indicate in which settings they are likely to be most useful and to point out some deficiencies in present methodologies. This will be done by attempting to answer a series of fundamental questions. Cell kinetics crucially affect many factors related to the timing of response after therapy. These include the time and rate of cell death, the rate of regression, the rate of reoxygenation, and the time to recurrence. Proliferation of surviving cells can also occur during gaps in treatment, whether the treatment be radiotherapy or chemotherapy, and whether the gaps are short (eg, between daily treatments) or longer (eg, a weekend; weeks between treatment courses; weeks between surgery and adjuvant radiotherapy or chemotherapy), l The end result of such proliferation is the partial repopulation of a tumor before treatment is ended. In other words, repopulation can compete with treatment-induced cell killing, reducing the effectiveness of the treatment. There