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Cellular senescence is a stress response elicited by different molecular insults. Senescence results in cell cycle exit and is characterised by multiple phenotypic changes such as the production of a bioactive secretome. Senescent cells accumulate during ageing and are present in cancerous and fibrotic lesions. Drugs that selectively kill senescent cells (senolytics) have shown great promise for the treatment of age-related diseases. Senescence plays paradoxical roles in cancer. Induction of senescence limits cancer progression and contributes to therapy success, but lingering senescent cells fuel progression, recurrence, and metastasis. In this review, we describe the intricate relation between senescence and cancer. Moreover, we enumerate how current anti-cancer therapies induce senescence in tumour cells and how senolytic agents could be deployed to complement anticancer therapies. "One-two punch" therapies aim to first induce senescence in the tumour followed by senolytic treatment to target newly exposed vulnerabilities in senescent tumour cells. "One-two punch" represents an emerging and promising new strategy in cancer treatment. Future challenges of "one -two punch" approaches include how to best monitor senescence in cancer patients to effectively survey their efficacy.

Invasive pink salmon (Oncorhynchus gorbuscha) has been present in variable, but low, numbers in Norwegian waters since c. 1960, but beginning in 2017 their numbers have exploded in rivers in northern Norway, with considerable numbers also recorded in rivers in southern Norway and other countries bordering the North Atlantic. Analysis of pink salmon scales from two rivers draining to the western Barents Sea showed declining growth during the first weeks after entering the sea, and some individuals even showed a pronounced growth arrest, based on detailed scale circulus analyses. This was followed by a period of growth increase and stability during late summer and autumn, which may reflect a transition to better food sources, as the fish migrate from coastal waters to the open ocean, and as they grow larger and can eat larger and more energy efficient food items. Growth declined to a minimum during winter. Fish body size at spawning was positively correlated with the distance from scale focus to the last winter circulus, as well as with the number of circuli. When dividing scale growth into three periods, better growth during the first period at sea was related to increased fish body length at spawning, but this early growth explained only a minor part (6%) of the variation in final body length. The reason for this may be large individual variation in growth combined with large mortality during the first weeks at sea. If mortality is selective, removing fish with poor growth may reduce a correlation between early growth and body size at spawning. Scale growth during late summer and early autumn explained more of the variation in fish length at spawning (27%). Hence, late summer and early autumn was likely an important period for marine growth and survival in the invasive pink salmon.

RigidTack™ is a newly developed implant for total temporary epiphyseodesis. The implant combines the technical advantages of the traditionally used rigid Blount-staples and the newer flexible eight-plates™. Thus, the implant is rigid like the Blount-staples, which may be a biomechanical advantage in temporary epiphyseodesis, and has an easy and guided implantation technique like the eight-plate™. As in eight-plates™, supposedly only two RigidTacks™ are sufficient for temporary epiphyseodesis compared to six Blount-staples in traditional treatment. The goal of this study was to compare Blount-staples and RigidTacks™ in regard to the total potential of growth arrest, the occurrence of postoperative implant-associated complications, secondary angular deformities, and central joint deformations. Twelve pigs were allocated in two groups (n = 6) for treatment of the proximal tibia. Total temporary epiphysiodesis was performed with either four Blount-staples or two RigidTacks™. Magnetic resonance imaging (MRI)-scans were performed before and 14 weeks after surgery, and the amount and distribution of growth arrest were evaluated by measuring the interphyseal distance in nine defined zones. Total temporary epiphysiodesis with two RigidTacks™ resulted in a similar amount of growth arrest as that of four Blount-staples. No significant coronal or sagittal angular deformities or joint deformities were observed in either group; however, one secondary loosening of a Blount-staple occurred. The study concluded that Blount-staples and RigidTacks™ are adequate implants for total temporary epiphysiodesis. Whether or not the precise implant-placement through the guided implantation technique of RigidTacks™ and a reduced number of implants indeed lead to a reduction of secondary angular deformities has to be investigated in further clinical trials. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:946-953, 2020.

Growth arrest-specific 6 (GAS6) protein plays a key role in processes related to proliferation, inflammation, angiogenesis, and atherosclerotic plaque formation. In addition, it has been reported that plasma levels of GAS6 are related to cancer prognosis and other relevant pathologies, such as heart failure or sepsis. We report here the first electrochemical immunoplatform for the determination of GAS6, which has demonstrated to be competitive with other available methodologies in terms of cost, simplicity, and decentralized application. The developed immunoplatform involves a sandwich immunoassay using magnetic microparticles (MBs) and uses amperometric detection at disposable screen-printed carbon electrodes (SPCEs). The MBs were modified with an antibody specific to GAS6 for its selective capture, which is further recognized by a biotinylated secondary antibody subsequently labeled with a streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The electrochemical detection was carried out using the hydroquinone (HQ)/H2O2 system. The developed bioplatform exhibits a great selectivity and low limit of detection (27 pg/mL) that allowed the determination of the GAS6 circulating level in plasma samples from patients suffering heart failure (HF) and diagnosed with pancreatic ductal adenocarcinoma (PDAC), as well as the determination of the target protein in raw secretomes of human colorectal cancer cell lines., This work is part of the POSITION-II project fundedby the ECSEL Joint Undertaking under grant numberEcsel-783132-Position-II-2017-IA;www.position-2.eu,and PCI2018-093067 (Spanish Ministerio de Ciencia eInnovación) to M.P. The financial support of PID2019-103899RB-I00 (Spanish Ministerio de Ciencia e Inno-vación) Research Project to S.C., PI17CIII/00045 andPI20CIII/00019 grants from the AES-ISCIII program toR.B. and the TRANSNANOAVANSENS-CM Program fromthe Comunidad de Madrid (Grant S2018/NMT-4349) toS.C., RTI2018-095672-B-I00 (Spanish Ministerio de Cienciae Innovación) to P.G.F.; Fundació la Marató de TV3 project081010toM.B.; researchprojectPI20/00625,fromtheAES-ISCIII/FEDER program, to P.N, are gratefully acknowl-edged. A. Montero-Calle acknowledges the support of theFPU predoctoral contracts by the Spanish Ministerio deEducación, Cultura y Deporte. G.S-F. is recipient of a pre-doctoral contract (grant number 1193818N) supported byThe Flanders Research Foundation (FWO). C. Muñoz-SanMartín acknowledges a predoctoral contract from Complutense University of Madrid. R.M. Torrente-Rodríguezacknowledges a Talento-Contract from Comunidad deMadrid (2019-T2/IND-15965).

Cellular senescence, a state of irreversible growth arrest triggered by various stressors, engages in a category of pathological processes, whereby senescent cells accumulate in mitotic tissues. Senolytics as novel medicine against aging and various diseases through the elimination of senescent cells has emerged rapidly in recent years. Exercise is a potent anti‐aging and anti‐chronic disease medicine, which has shown the capacity to lower the markers of cellular senescence over the past decade. However, whether exercise is a senolytic medicine for aging and various diseases remains unclear. Here, we have conducted a systematic review of the published literature studying the senolytic effects of exercise or physical activity on senescent cells under various states in both human and animal models. Exercise can reduce the markers of senescent cells in healthy humans, while it lowered the markers of senescent cells in obese but not healthy animals. The discrepancy between human and animal studies may be due to the relatively small volume of research and the variations in markers of senescent cells, types of cells/tissues, and health conditions. These findings suggest that exercise has senolytic properties under certain conditions, which warrant further investigations., Cellular senescent upregulates certain markers such as p16INK4a, p21Cip1, SA‐beta‐Gal, and/or SASP, which can also be shown in accelerated aging animals. This review discusses by using human and experimental laboratory animal studies to show how exercise attenuates all these senescent markers and serves as senolytic medicine.

Members of the growth arrest–specific 2 (GAS2) protein family consist of a putative actin‐binding (CH) domain and a microtubule‐binding (GAR) domain and are considered miniversions of spectraplakins. There are four members in the GAS2 family, viz. GAS2, GAS2L1, GAS2L2 and GAS2L3. Although GAS2 is defined as a family of growth arrest–specific proteins, the significant differences in the expression patterns, interaction characteristics and biological issues or diseases among the different GAS2 family members have not been systemically reviewed to date. Therefore, we summarized the available evidence on the structures and functions of GAS2 family members. This review facilitates a comprehensive molecular understanding of the involvement of the GAS2 family members in an array of biological processes, including cytoskeleton reorganization, cell cycle, apoptosis and cancer development., The GAS2 (growth arrest–specific 2) family contains a putative actin‐binding (CH) domain and a microtubule‐binding (GAR) domain There are four members in the GAS2 protein family, namely GAS2, GAS2L1, GAS2L2 and GAS2L3. Different structural characteristics of GAS2 family members lead to the distinct ways for the binding with cytoskeletal proteins, and the modulation of crosslinking between actin and microtubule, which may be the mechanistic basis of versatile role of GAS2 family in cell cycle, apoptosis or cancer.

With the heightened popularity of childhood sporting activity, the number of paediatric anterior cruciate ligament (ACL) ruptures has increased. Management of these injuries presents a particular challenge due to the open femoral and tibial growth plates. Physeal damage has the potential to cause angular deformity or length discrepancy. This review was conducted to determine the best way to treat this injury. A primary search of Ovid MEDLINE (1 October 2017) used the terms: (ACL or anterior cruciate ligament) and (young or child or children or pediatric or immature or pre-pubescent). Titles/Abstracts of 369 articles were screened for relevance. A total of 217 were excluded, leaving 152 articles for full-paper retrieval. Of these, 9 articles remained with one further article identified during cross-referencing; 10 papers (1 level 2 and 9 level 3) were included for analysis. Comparative studies investigating surgical (140 knees) versus conservative (110 knees) treatment provide evidence in favour of the former, in reducing instability and meniscal tears and improving return to previous activity. Of the papers analysed (163 reconstructions), there was only one case of growth arrest (0.6%) and no cases of length discrepancy. In those studies investigating early (218 patients) versus delayed (140 patients) reconstruction, medial meniscal tears and chondral injuries occurred more frequently in the delayed group. To conclude, for children, there is level 2/3 evidence that early operative ACL reconstruction offers the best chance of a return to pre-injury sporting activity and minimises the risks of further structural damage. Iatrogenic growth disturbance remains a rare but worrying complication.

When seeds are exposed to drought and salinity during germination, newly germinated embryos stop growth and enter a quiescent state called postgerminative growth (PGG) arrest. PGG arrest protects embryos from the stress, but it is not known how PGG is restored from the arrest when stress is eased. In this study, we show that under stress- or abscisic acid-induced PGG arrest conditions, Arabidopsis thaliana Raf-type protein kinase 22 (AtRaf22) overexpression accelerated photoautotrophic seedling establishment, whereas atraf22 knockout mutations enhanced the arrest. Furthermore, when the stress intensity was reduced subsequently, AtRaf22 overexpression plants resumed growth and accomplished photoautotrophic transition much faster than the knockout or wild-type plants. These results suggest that AtRaf22 activity is important for maintaining growth capacity during stress-induced PGG arrest, which is most likely critical for competitive growth when the stress subsides and plants resume growth. Such a factor has not been reported before.

The use of sponges in biotechnological processes is limited by the supply problem, and sponge biomass production is becoming a current topic of research. The distinction between characteristics for growth and growth arrest is also important for environmental monitoring. In this study, we analyze the morphology of the digitate outgrowths from the sponge Haliclona sp. The sponge Haliclona sp. was successfully cultivated for 14 months in a closed system. The morphological characterization of growth arrest was performed after submitting explants to starvation-stress for approximately 2 weeks, to correlate morphology with growth and growth arrest. The digitate outgrowth showed three distinct regions: mature (MR), transition (TR) and immature (IR). Our data suggest a growth developmental program, with collagen fascicles guiding axial growth in IR, followed by progressive development of choanocyte chambers and large aquiferous systems at the more mature proximal region (choanosome). The intercalation of choanocyte chambers and small aquiferous systems inside collagen fascicles previously originated at the IR region can be responsible for thickening expansion and conversion of the collagen fascicles into columnar choanosome in MR. The growth arrest after starvation-stress assay showed morphological changes in the IR corroborating collagen in the extreme tip of the digitate outgrowth as an important role in guiding of axial growth of Haliclona sp. The identification of distinct morphologies for growth and growth arrest suggest a growth developmental program, and these data could be useful for further investigations addressing sponge biomass gain and environmental monitoring.

Methylation is a prevalent post-transcriptional modification that occurs in almost all RNA species. NSUN2, a nucleolar RNA methyltransferase, has been shown to methylate mRNAs encoding factors that control cell division and growth arrest, thereby affecting their stability and/or translation. Here, the author summarizes the recent progress in understanding NSUN2-mediated mRNA methylation and its implications in cell proliferation and senescence. WIREs RNA 2016, 7:838-842. doi: 10.1002/wrna.1380 For further resources related to this article, please visit the WIREs website.

It is widely accepted that there exists a "resting" or "quiescent" state where a growing cell leaves the cell cycle to enter what is often called the "G0-phase." I propose that there is no biological reality to the "G0-phase." The experimental basis for proposing a G0-phase is re-examined and re-analyzed here showing that the G0-phase is an anthropomorphic construct with no biological reality.

Dietary agents are receiving much attention for the chemoprevention of cancer. While curcumin is known to influence several pathways and affect tumor growth in vivo, carnitin and its congeners play a variety of important metabolic functions: are involved in the oxydation of long-chain fatty acids, regulate acyl-CoA levels and influence protein activity and stability by modifying the extent of protein acetylation. In this study we evaluated the efficacy of carnitines in the prevention of cancer development using the 1,2,-dimethylhydrazine (DMH)-induced colon carcinogenesis model. We also assessed whether their combination was able to give rise to increased protection from cancer development. Mice treated with DMH were dosed orally with curcumin and/or carnitine and acylcarnitines for 20 weeks. At the end of the treatment colon samples were collected, and scored for multiple ACF and adenomas. We observed that carnitine and acyl-carnitines had same, if not higher, efficacy than curcumin alone in inhibiting the formation of neoplastic lesions induced by DMH treatment. Interestingly, the combination of curcumin and acetyl-L-carnitine was able to fully inhibit the development of advanced adenoma lesions. Our data unveil the antitumor effects of carnitines and warrant additional studies to further support the adoption of carnitines as cancer chemopreventative agents.

Despite clinical efforts to treat growth disturbances only little is known about the growth potential of the different zones of the growth plate. The aim of this study was to investigate the growth potential of different zones of the growth plate. A total of 20 New Zealand White rabbits were used for this experiment. The right and left ulna of each animal were used resulting in a total of 40 ulnae. Animals were assigned into five groups. In groups I and II resection of the metaphyseal (n = 12) or the epiphyseal (n = 6) segment of the growth plate was performed. In group III resection of the growth plate and re-implantation was performed (n = 6). In group IV the growth plate was resected and re-implanted after a 180° rotation (n = 6). Animals in group V served as controls. Histologic and radiologic examinations were performed to evaluate the growth process at 1, 2, 4, and 12 weeks following surgery. In group I, III, and IV temporary growth disturbance which was compensated within a short time was observed. Resection of the epiphyseal part resulted in growth arrest of the distal ulna in combination with normal growth of the radius which led to and valgus deformity of the limb. The results of this study indicate the importance of the reserve zone for the functioning of the growth plate.

Background Notch pathway signaling has critical roles in differentiation, proliferation and survival, and has oncogenic or tumor suppressor effects in a variety of malignancies. The goal of this study was to evaluate the effects of Notch activation on human neuroblastoma cells.

Preeclampsia (PE) is a complicated obstetric complication characterized by increased blood pressure and decreased trophoblast invasion. The growth arrest-specific 6 (Gas6) protein is known to induc...

The growth of Kluyveromyces thermotolerans and Torulaspora delbrueckii was examined in mixed cultures with Saccharomyces cerevisiae in YPD modified for wine fermentations. Although the three yeasts had similar maximum specific growth rates in these fermentations, K. thermotolerans and T. delbrueckii arrested growth earlier than S. cerevisiae, thereby obtaining lower stationary phase cell concentrations than S. cerevisiae. Various single and mixed culture fermentations with the three yeasts were carried out in order to find an explanation for this phenomenon. The early growth arrests of K. thermotolerans and T. delbrueckii were absent in single cultures of the two yeasts, and they seemed to be due neither to nutrient limitations nor to the presence of growth-inhibitory compounds. Rather, they seemed to be due to a cell-cell contact mechanism dependent on the presence of viable S. cerevisiae cells at high concentrations. These results contribute to an increased understanding of why K. thermotolerans and T. delbrueckii arrest growth before S. cerevisiae during wine fermentations.

Ligands that elevate cAMP through Gs-coupled GPCR activation have profound effects on the differentiation of neuroendocrine cells. Using the PC12 cell subclone NS-1, we found that cAMP-induced neur...

Previously we showed that TCERG1 inhibits the growth arrest and transactivation functions of C/EBPα, through a mechanism that requires the relocalization of TCERG1 to sites of C/EBPα occupancy in the nucleus. TCERG1 contains a unique QA repeat domain, for which no function has been assigned, as well as 3 WW domains within the N-terminal half of TCERG1 which has been shown previously to mediate its relocalization. These domains were explored for their roles in mediating the inhibitory and relocalization activities of TCERG1. While mutations of the WW domains were without effect, deletion of the QA repeat domain in TCERG1 prevented its relocalization in the nucleus (assessed by confocal microscopy), and abrogated its ability to repress both the growth arrest and transactivation functions of C/EBPα. Reducing the number of QA repeats from 38 to 20 had no impact on the activities of TCERG1, while further reduction to 10 resulted in a significant loss of relocalization ability and inhibitory activity towards C/...

Zinc-alpha(2)-glycoprotein (Znalpha(2)gp) is widely distributed in body fluids and epithelia. Its expression in stratified epithelia increases with differentiation. We previously showed that Zn alpha(2)gp has ribonuclease activity, and that squamous tumor cells grown on a matrix of Znalpha(2)gp were growth-inhibited. Here we demonstrate, both by adding Znalpha(2)gp to the culture medium and, more unequivocally, by stably transfecting SiHa cells with Znalpha(2)gp cDNA, that the introduction of Znalpha(2)gp into SiHa tumor cells reduces proliferation. In response to Znalpha(2)gp, we find an accumulation of the cell population in G(2)/M by flow cytometry, paralleling the reduction of proliferation. In order to distinguish growth inhibition by cell cycle arrest from that produced by apoptosis or differentiation, we examine by RT-PCR how Znalpha(2)gp affects the expression of genes commonly used as markers of these properties. No changes are observed for PCNA, p53, c-myc, or bcl-2. Only cdc2 expression responds to Znalpha(2)gp, with a reduction of up to over a factor of two. Cdc2 is the only cyclin-dependent kinase regulating the G(2)/M transition without redundancy and is required as a rate-limiting step in the cell cycle. Its increased expression has been directly linked to increased proliferation and decreased differentiation of advanced tumors; conversely, its downregulation by Znalpha(2)gp might hinder tumor progression. J. Cell. Biochem. Suppl. 36: 162-169, 2001.

Expression of retinoic acid receptor beta (RARbeta) is reported to be absent or down-regulated in oral squamous cell carcinomas. Recently, we found that the growth-inhibitory effect of 9-cis-retinoic acid (9CRA) on oral squamous cell carcinoma may depend on the expression levels of endogenous RARbeta. In order to clarify the role of RARbeta in growth and differentiation, we transfected RARbeta expression vector into oral squamous carcinoma cell lines, HSC-4 and Ho-1-N-1. Both RARbeta-transfected cell lines displayed growth inhibition. Moreover, RARbeta-transfected clones underwent morphological changes, and RARbeta-transfected HSC-4 clones underwent apoptosis even in the absence of 9CRA treatment. In contrast, RARbeta-transfected Ho-1-N-1 clones exhibited cell cycle arrest without undergoing apoptosis initially; however, apoptosis was induced in these cells after 6 days of 9CRA treatment. RARalpha and RARgamma expression was reduced at both the protein and mRNA levels in RARbeta transfectants, whereas the expression of retinoid X receptor alpha (RXRalpha) was not altered. RARb transfectants exhibited alterations in the levels of cell cycle-associated proteins, histone acetyltransferase (HAT) and apoptosis-associated proteins. After 6 days of 9CRA treatment, RARbeta transfectants overexpressed Waf1 / Cip1 / Sdi1 / p21, Kip1 / p27, chk1, p300 / CBP, BAX, Bak, Apaf 1, caspase 3 and caspase 9. Conversely, E2F1, cdc25B and HDAC1 were down-regulated in these transfectants. In addition, histone H4 acetylation was induced in RARb transfectants. These findings suggest that histone acetylation mediated by histone acetyltransferase and p300 / CBP may play a role in the growth arrest and apoptosis induced by RARbeta transfection in oral squamous cell carcinoma.

Interferon-gamma (IFN-gamma) induces growth arrest and apoptosis of tumor cells but the mechanisms for these functions are unknown. Recently, gut-enriched krüppel-like factor (GKLF) was found to possess similar biological properties. Treatment of HT-29 cells with IFN-gamma inhibited cell proliferation and induced apoptosis, the effect was found to associate with GKLF expression. IFN-gamma stimulates GKLF mRNA and protein levels in a dose- and time-dependent manner and this process is independent of p53, occurs rapidly and does not require de novo protein synthesis indicating that GKLF is an immediate-early IFN-gamma-responsive gene. Moreover, overexpression of GKLF results in similar effect as IFN-gamma suggesting that GKLF may function as a downstream target of IFN-gamma.

Proliferating cell nuclear antigen (PCNA) functions as a processivity factor for DNA polymerase delta, and is expressed at high levels in growing normal and tumor cells. To clarify the relationship between cell proliferation and PCNA expression, we generated NIH-3T3 cells that overexpress PCNA and analyzed the phenotype of these cells. The resulting 3T3-PCNA cells, which overexpressed PCNA, were found to proliferate beyond the saturation density of the parental NIH-3T3 cells. Although NIH-3T3 cell proliferation is arrested under serum starvation conditions, 3T3-PCNA cell proliferation is not arrested by serum starvation. The expression levels of cdk2, cdk4 and cdk6 were the same in 3T3-PCNA and NIH-3T3 cells. The activity of cdk4 was identical for both cell types. However, the activity of cdk2 was higher in serum-starved 3T3-PCNA cells than in NIH-3T3 cells, although the expression of cyclin E decreased in both types of cells, suggesting that increases in cdk2 activity are related to negation of growth arrest in 3T3-PCNA cells. These results indicate that increases in PCNA expression lead to the disruption of growth control and may lead to malignant transformation.

Objectives Harris lines (HLs) are defined as transverse, mineralized lines associated with temporary growth arrest. In paleopathology, HLs are used to reconstruct health status of past populations. However, their etiology is still obscure. The aim of this article is to test the reliability of HLs as an arrested growth marker by investigating their incidence on human metrical parameters. Methods The study was performed on 69 individuals (28 adults, 41 subadults) from the Dendermonde plague cemetery (Belgium, 16th century). HLs were rated on distal femora and both ends of tibiae. Overall prevalence and age-at-formation of each detected lines were calculated. ANOVA analyses were conducted within subadult and adult samples to test if the presence of HLs did impact size and shape parameters of the individuals. Results At Dendermonde, 52% of the individuals had at least one HL. The age-at-formation was estimated between 5 and 9 years old for the subadults and between 10 and 14 years old for the adults. ANOVA analyses showed that the presence of HLs did not affect the size of the individuals. However, significant differences in shape parameters were highlighted by HL presence. Subadults with HLs displayed slighter shape parameters than the subadults without, whereas the adults with HLs had larger measurements than the adults without. Conclusions The results suggest that HLs can have a certain impact on shape parameters. The underlying causes can be various, especially for the early formed HLs. However, HLs deposited around puberty are more likely to be physiological lines reflecting hormonal secretions. Am. J. Hum. Biol., 2016. © 2016 Wiley Periodicals, Inc.

This brief overview outlines recent progress in our understanding of the regulation of cell population size, focusing on some important developments in cell cycle control and the recognition of the importance of growth arrest and cell death. Histopathologists, and others with an interest in tissue architecture, have much to offer to those who study the biochemical and molecular processes of proliferation, growth arrest and cell death, and these processes are unlikely to be understood simply by analysis of in vitro systems and cell lines. Such biochemical and histological information may well feed back into clinical medicine in terms of new approaches and techniques, new reagents and new paradigms. With regard to the application of measures of proliferation, growth arrest and cell death as prognostic factors or other diagnostic tools, we are sceptical. Methods for assessing cell proliferation seem unlikely to be implemented widely in practice since there is little direct evidence that they are really an improvement on conventional histological assessment, optimally employed. But, there again, we may be proved wrong! In particular, it may be that, if carefully employed, assays that integrate information about death, growth arrest and proliferation may be clinically valuable.

A frequent problem in cancer therapy is the emergence of resistant cells. The nitrogen mustard-resistant cell line Raji-HN2 was used to investigate the relationship between drug resistance and expression of a variety of genes which are inducible by various types of DNA damage including radiation. It ws found that only GADD153, a member of the CCAAT enhancer binding protein (C/EBP) family of transcription factors, showed increased expression in these drug-resistant cells. Increased GADD153 expression is intriguing since this gene is induced in non-resistant cells by HN2, as well as other drugs, certain types of radiation, and growth arrest. Since GADD153 is a transcription factor, its overexpression in resistant cells may modulate the expression of other genes as well. It was also found that a short G-tract-containing transcript was also increased in the Raji-HN2 cells. The nature of this transcript and its relevance to drug resistance in Raji-HN2 are unknown. © Wiley-Liss, Inc.

Old and new data on the size of the human parietal bone are presented. Attention is drawn to zonal changes in the configuration of the bones, particularly in fetuses and newborn babies, that almost certainly indicate phasic variations in the growth rate of the baby, and it is suggested that the estimation of the size of the bone where these abnormal zones occur may be a guide as to the intrauterine age of the child when the alteration in growth occurred. Parietal bone size could also be a help in describing local and general skeletal dysplasias.

The differentiation of 3T3 T proadipocytes is preceded by growth arrest at a state in the G1 phase of the cell cycle (GD) which is distinct from other G1 growth arrest states including those induced by serum deprivation (GS) or nutrient deprivation (GN) (Scott et al., 1982). We now report that the GD, GS, and GN arrest states are also distinct in their topography in G1. This conclusion was derived from kinetic studies which measured the time required for cells arrested at various G1 states to synthesize DNA and from studies on the ability of GD-, GS-, or GN-arrested cells to be converted from one arrest state to another in the absence of DNA synthesis. The results suggest that relative to the start of the G1 phase of the cell cycle, the following arrest state topography exists: GD, GS, GN.

The present analysis represents a follow-up to a previous experimental study in which facial shortening obtained in rats by septum removal produced also shortening of the molar roots. In the present study relative root length was compared in short-faced as against long-faced dogs and significant correlations between relative facial length and dental root length were found. Root shortening in the maxilla of short-faced dogs clusters around the areas of the premaxillary-maxillary suture and the maxillary-palatine suture. For the mandible it shifts one tooth more distally and is of lower statistical significance. This distribution seems to tie in with the greater growth arrest in the above sutural areas in the maxilla of short-faced dogs and the lesser growth arrest of their mandible.