Cyfip1 is a putative invasion suppressor in epithelial cancers.

Identification of bona fide tumor suppressors is often challenging because of the large number of genetic alterations present in most human cancers. To evaluate candidate genes present within chromosomal regions recurrently deleted in human cancers, we coupled high-resolution genomic analysis with a two-stage genetic study using RNA interference (RNAi). We found that Cyfip1, a subunit of the WAVE complex, which regulates cytoskeletal dynamics, is commonly deleted in human epithelial cancers. Reduced expression of CYFIP1 is commonly observed during invasion of epithelial tumors and is associated with poor prognosis in this setting. Silencing of Cyfip1 disturbed normal epithelial morphogenesis in vitro and cooperated with oncogenic Ras to produce invasive carcinomas in vivo. Mechanistically, we have linked alterations in WAVE-regulated actin dynamics with impaired cell-cell adhesion and cell-ECM interactions. Thus, we propose Cyfip1 as an invasion suppressor gene.

Exploiting Ambipolarity in Graphene Field-Effect Transistors for Novel Designs on High-Frequency Analog Electronics.

Exploiting ambipolar electrical conductivity based on graphene field-effect transistors has raised enormous interest for high-frequency (HF) analog electronics. Controlling the device polarity, by biasing the graphene transistor around the vertex of the V-shaped transfer curve, enables to redesign and highly simplify conventional analog circuits, and simultaneously to seek for multifunctionalities, especially in the HF domain. This study presents new insights for the design of different HF applications such as power amplifiers, mixers, frequency multipliers, phase shifters, and modulators that specifically leverage the inherent ambipolarity of graphene-based transistors.

Toward a realistic in silico abdominal phantom for QSM.

PURPOSE: QSM outside the brain has recently gained interest, particularly in the abdominal region. However, the absence of reliable ground truths makes difficult to assess reconstruction algorithms, whose quality is already compromised by additional signal contributions from fat, gases, and different kinds of motion. This work presents a realistic in silico phantom for the development, evaluation and comparison of abdominal QSM reconstruction algorithms. METHODS: Synthetic susceptibility and R 2 * $$ {R}_2^{\ast } $$ maps were generated by segmenting and postprocessing the abdominal 3T MRI data from a healthy volunteer. Susceptibility and R 2 * $$ {R}_2^{\ast } $$ values in different tissues/organs were assigned according to literature and experimental values and were also provided with realistic textures. The signal was simulated using as input the synthetic QSM and R 2 * $$ {R}_2^{\ast } $$ maps and fat contributions. Three susceptibility scenarios and two acquisition protocols were simulated to compare different reconstruction algorithms. RESULTS: QSM reconstructions show that the phantom allows to identify the main strengths and limitations of the acquisition approaches and reconstruction algorithms, such as in-phase acquisitions, water-fat separation methods, and QSM dipole inversion algorithms. CONCLUSION: The phantom showed its potential as a ground truth to evaluate and compare reconstruction pipelines and algorithms. The publicly available source code, designed in a modular framework, allows users to easily modify the susceptibility, R 2 * $$ {R}_2^{\ast } $$ and TEs, and thus creates different abdominal scenarios.

Community Health Workers in Early Childhood Well-Child Care for Medicaid-Insured Children: A Randomized Clinical Trial.

Importance: An intervention model (the Parent-focused Redesign for Encounters, Newborns to Toddlers; the PARENT intervention) for well-child care that integrates a community health worker into preventive care services may enhance early childhood well-child care. Objective: To examine the effectiveness of the PARENT intervention vs usual care for parents with children younger than 2 years of age. Design, Setting, and Participants: A cluster randomized clinical trial was conducted between March 2019 and July 2022. Of the 1283 parents with a child younger than 2 years of age presenting for a well-child visit at 1 of the 10 clinic sites (2 federally qualified health centers in California and Washington) approached for trial participation, 937 were enrolled. Intervention: Five clinics implemented the PARENT intervention, which is a team-based approach to care that uses a community health worker in the role of a coach (ie, health educator) as part of the well-child care team to provide comprehensive preventive services, and 5 clinics provided usual care. Main Outcomes and Measures: There were 2 primary outcomes: score for parent-reported receipt of recommended anticipatory guidance during well-child visits (score range, 0-100) and emergency department (ED) use (proportion with ≥2 ED visits). The secondary outcomes included psychosocial screening, developmental screening, health care use, and parent-reported experiences of care. Results: Of the 937 parents who were enrolled, 914 remained eligible to participate (n = 438 in the intervention group and n = 476 in the usual care group; 95% were mothers, 73% reported Latino ethnicity, and 63% reported an annual income <$30 000). The majority (855/914; 94%) of the children (mean age, 4.4 months at parental enrollment) were insured by Medicaid. Of the 914 parents who remained eligible and enrolled, 785 (86%) completed the 12-month follow-up interview. Parents of children treated at the intervention clinics (n = 375) reported receiving more anticipatory guidance than the parents of children treated at the usual care clinics (n = 407) (mean score, 73.9 [SD, 23.4] vs 63.3 [SD, 27.8], respectively; adjusted absolute difference, 11.01 [95% CI, 6.44 to 15.59]). There was no difference in ED use (proportion with ≥2 ED visits) between the intervention group (n = 376) and the usual care group (n = 407) (37.2% vs 36.1%, respectively; adjusted absolute difference, 1.2% [95% CI, -5.5% to 8.0%]). The effects of the intervention on the secondary outcomes included a higher amount of psychosocial assessments performed, a greater number of parents who had developmental or behavioral concerns elicited and addressed, increased attendance at well-child visits, and greater parental experiences with the care received (helpfulness of care). Conclusions and Relevance: The intervention resulted in improvements in the receipt of preventive care services vs usual care for children insured by Medicaid by incorporating community health workers in a team-based approach to early childhood well-child care. Trial Registration: ClinicalTrials.gov Identifier: NCT03797898.

On-Line Preconcentration and Simultaneous Determination of Cu and Mn in Water Samples Using a Minicolumn Packed with Sisal Fiber by MIP OES.

An on-line preconcentration system for the simultaneous determination of Copper (Cu) and manganese (Mn) in water samples was developed and coupled to a microwave-induced plasma optical emission spectrometer (MIP OES). The flow injection system was designed with a minicolumn packed with sisal fiber (Agave sisalana). A multivariate experimental design was performed to evaluate the influence of pH, preconcentration time, and eluent concentration. Optimal conditions for sample preparation were pH 5.5, preconcentration time was 90 s, and HCl 0.5 mol L-1 was the eluent. The main figures of merit were detection limits 3.7 and 9.0 µg L-1 for Cu and Mn, respectively. Precision was expressed as a relative standard deviation better than 10%. Accuracy was evaluated via spiked recovery assays with recoveries between 75-125%. The enrichment factor was 30 for both analytes. These results were adequate for water samples analysis for monitoring purposes. The preconcentration system was coupled and synchronized with the MIP OES nebulizer to allow simultaneous determination of Cu and Mn as a novel sample introduction strategy. The sampling rate was 20 samples/h. Sisal fiber resulted an economical biosorbent for trace element preconcentration without extra derivatization steps and with an awfully time of use without replacement complying with the principles of green analytical methods.

The acid-base and redox properties of menaquinone MK-4, MK-7, and MK-9 (vitamin K2) in DMPC monolayers on mercury.

The acid-base and redox properties of the menaquinones MK-4, MK-7, and MK-9 (vitamin K2) have been studied in DMPC monolayers on mercury electrodes. The monolayers were prepared by adhesion-spreading of menaquinone-spiked DMPC liposomes on a stationary mercury drop electrode. All three menaquinones possess [Formula: see text] constants outside the experimentally accessible range, i.e., they are higher than about 12. The standard potentials of MK-4, MK-7, and MK-9 in the DMPC monolayers are very similar, i.e., 0.351, 0.326, and 0.330 V (corresponding to the biochemical standard potentials - 0.063, - 0.088, and - 0.085 V).

Control of flowering and storage organ formation in potato by FLOWERING LOCUS T.

Seasonal fluctuations in day length regulate important aspects of plant development such as the flowering transition or, in potato (Solanum tuberosum), the formation of tubers. Day length is sensed by the leaves, which produce a mobile signal transported to the shoot apex or underground stems to induce a flowering transition or, respectively, a tuberization transition. Work in Arabidopsis, tomato and rice (Oryza sativa) identified the mobile FLOWERING LOCUS T (FT) protein as a main component of the long-range 'florigen', or flowering hormone, signal. Here we show that expression of the Hd3a gene, the FT orthologue in rice, induces strict short-day potato types to tuberize in long days. Tuber induction is graft transmissible and the Hd3a-GFP protein is detected in the stolons of grafted plants, transport of the fusion protein thus correlating with tuber formation. We provide evidence showing that the potato floral and tuberization transitions are controlled by two different FT-like paralogues (StSP3D and StSP6A) that respond to independent environmental cues, and show that an autorelay mechanism involving CONSTANS modulates expression of the tuberization-control StSP6A gene.

Tumor-derived exosomes are enriched in ΔNp73, which promotes oncogenic potential in acceptor cells and correlates with patient survival.

Tumor-derived exosomes are emerging as local and systemic cell-to-cell mediators of oncogenic information through the horizontal transfer of mRNAs, microRNAs and proteins during tumorigenesis. The exosomal content has been described as biologically active when taken up by the recipient cell. Identifying the specific molecular cargo of exosomes will help to determine their function in specific steps of the tumorigenic process. Here we evaluate whether ΔNp73 is selectively packaged in tumor-derived exosomes, its function in the acceptor cells in vitro and in vivo and its prognosis potential in cancer. ΔNp73 messenger is enriched in tumor-derived exosomes, suggesting its active sorting in these microvesicles. We observed the transmission of this exosome cargo to different cell types and how it confers proliferation potential and chemoresistance to the acceptor cells in vitro and in animal models. Finally, our data support the potential prognostic value of exosomal ΔNp73 in colon cancer patients.

Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer.

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content.

Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells.

Snail1 is a transcriptional factor that plays an important role in epithelial-mesenchymal transition and in the acquisition of invasive properties by epithelial cells. In colon tumors, Snail1 expression in the stroma correlates with lower specific survival of cancer patients. However, the role(s) of Snail1 expression in stroma and its association with patients' survival have not been determined. We used human primary carcinoma-associated fibroblasts (CAFs) or normal fibroblasts (NFs) and fibroblast cell lines to analyze the effects of Snail1 expression on the protumorigenic capabilities in colon cancer cells. Snail1 expression was higher in CAFs than in NFs and, as well as α-SMA, a classic marker of activated CAFs. Moreover, in tumor samples from 50 colon cancer patients, SNAI1 expression was associated with expression of other CAF markers, such as α-SMA and fibroblast activation protein. Interestingly, coculture of CAFs with colon cells induced a significant increase in epithelial cell migration and proliferation, which was associated with endogenous SNAI1 expression levels. Ectopic manipulation of Snail1 in fibroblasts demonstrated that Snail1 expression controlled migration as well as proliferation of cocultured colon cancer cells in a paracrine manner. Furthermore, expression of Snail1 in fibroblasts was required for the coadjuvant effect of these cells on colon cancer cell growth and invasion when coxenografted in nude mice. Finally, cytokine profile changes, particularly MCP-3 expression, in fibroblasts are put forward as mediators of Snail1-derived effects on colon tumor cell migration. In summary, these studies demonstrate that Snail1 is necessary for the protumorigenic effects of fibroblasts on colon cancer cells.

Assessing community-level impacts of and responses to stay at home orders: The King County COVID-19 community study.

BACKGROUND: At the beginning of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) of unprecedented scope and duration were implemented to limit community spread of COVID-19. There remains limited evidence about how these measures impacted the lived experience of affected communities. This study captured the early impacts and coping strategies implemented in King County, Washington, one of the first U.S. communities impacted by COVID-19. METHODS: We conducted a cross-sectional web-based survey of 793 English- and Spanish-speaking adult King County residents from March 18, 2020 -May 30, 2020, using voluntary response sampling. The survey included close- and open-ended questions on participant demographics, wellbeing, protective actions, and COVID-19-related concerns, including a freeform narrative response to describe the pandemic's individual-, family- and community-level impacts and associated coping strategies. Descriptive statistics were used to analyze close-ended questions, and qualitative content analysis methods were used to analyze free-form narrative responses. RESULTS: The median age of participants was 45 years old, and 74% were female, 82% were White, and 6% were Hispanic/Latinx; 474 (60%) provided a qualitative narrative. Quantitative findings demonstrated that higher percentages of participants engaged in most types of COVID-19 protective behaviors after the stay-at-home order was implemented and schools and community spaces were closed, relative to before, and that participants tended to report greater concern about the pandemic's physical health or healthcare access impacts than the financial or social impacts. Qualitative data analysis described employment or financial impacts (56%) and vitality coping strategies (65%), intended to support health or positive functioning. CONCLUSIONS: This study documented early impacts of the COVID-19 pandemic and the NPIs implemented in response, as well as strategies employed to cope with those impacts, which can inform early-stage policy formation and intervention strategies to mitigate the negative impacts. Future research should explore the endurance and evolution of the early impacts and coping strategies throughout the multiyear pandemic.

Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients.

Tumor epithelial cells within a tumor coexist with a complex microenvironment in which a variety of interactions between its various components determine the behavior of the primary tumors. Cancer-associated fibroblasts (CAF) and M2 macrophages, characterized by high expression of different markers, including α-SMA, FSP1 and FAP, or CD163 and DCSIGN, respectively, are involved in the malignancy of different tumors. In the present study, expression of the above markers in CAF and M2 macrophages was analyzed using RT-PCR and immunohistochemistry in the normal mucosa and tumor tissue from a cohort of 289 colorectal cancer patients. Expression of CAF and M2 markers is associated with the clinical outcome of colorectal cancer patients. Moreover, the combination of CAF and M2 markers identifies three groups of patients with clear differences in the progression of the disease. This combined variable could be a decisive factor in the survival of advanced-stage patients. Taken together, these analyses demonstrate the prognostic involvement of interrelationships between DCSIGN, CD163, α-SMA, FSP1 and FAP markers in the survival of colon cancer patients.

KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects in colon cancer cells.

KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory role in development and physiology. Here, we show that human JMJD3 expression is induced by the active vitamin D metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this hormone. 1,25(OH)(2)D(3) activates the JMJD3 gene promoter and increases the level of JMJD3 RNA in human cancer cells. JMJD3 upregulation was strictly dependent on vitamin D receptor (VDR) expression and was abolished by cycloheximide. In SW480-ADH colon cancer cells, JMJD3 knockdown or expression of an inactive mutant JMJD3 fragment decreased the induction by 1,25(OH)(2)D(3) of several target genes and of an epithelial adhesive phenotype. Moreover, JMJD3 knockdown upregulated the epithelial-to-mesenchymal transition inducers SNAIL1 and ZEB1 and the mesenchymal markers fibronectin and LEF1, while it downregulated the epithelial proteins E-cadherin, Claudin-1 and Claudin-7. Additionally, JMJD3 knockdown abolished the nuclear export of ß-catenin and the inhibition of ß-catenin transcriptional activity caused by 1,25(OH)(2)D(3). Importantly, the expression of JMJD3 correlated directly with that of VDR and inversely with that of SNAI1 in a series of 96 human colon tumours. Our results indicate for the first time that an epigenetic gene coding for a histone demethylase such as JMJD3 is a VDR co-target that partially mediates the effects of 1,25(OH)(2)D(3) on human colon.

Should we think about green or white analytical chemistry? Case study: Accelerated sample preparation using an ultrasonic bath for the simultaneous determination of Mn and Fe in beef.

Green Analytical Chemistry (GAC) metrics include a variety of criteria, such as the regent amounts and toxicity, energy consumption, generated waste, among others. The analytical greenness metric (AGREE) and its variant for sample preparation (AGREEprep) cover different aspects that contribute to the environmental sustainability of sample preparation. White Analytical Chemistry (WAC) considers not only environmental aspects but also analytical and practical aspects with a holistic vision based on a Red-Green-Blue color model. A case study is presented to assess the green and white profile of a method based on ultrasound-assisted extraction and determination of Mn and Fe in beef using microwave-induced plasma atomic emission spectroscopy (MP AES). The method was validated and resulted simple, fast without external heating using diluted acids. It was concluded that we should think in green sample preparation with the AGREEprep tool, as well as in white holistic assessments (WAC) as both constitute complementary tools.

Effect of Adding Bovine Skin Gelatin Hydrolysates on Antioxidant Properties, Texture, and Color in Chicken Meat Processing.

(1) Background: Phosphates are used in the food industry to improve water retention and product quality. However, when consumed in excess, they can be harmful to health. Instead, bovine skin gelatin hydrolysates present health benefits such as being a rejuvenating agent, stimulating collagen production, and improving food quality, in addition to being a source of protein. The effect of the addition of bovine skin gelatin hydrolysates on the texture and color of thermally processed chicken meat (boiled type) and antioxidant activity was evaluated. (2) Methods: Hydrolysates were prepared with subtilisin with the degree of hydrolysis being 6.57 and 13.14%, which were obtained from our previous study. (3) Results: The hydrolysates improved the firmness of the meat matrix compared to the control. Additionally, the hydrolysate with a 13.14% degree of hydrolysis reached the same firmness (p > 0.05) as the commercial ingredient sodium tripolyphosphate at its maximum limit allowed in the food industry when it was applied at 5% (w/w meat) in the meat matrix, improving firmness over the control by 63%. Furthermore, both hydrolysates reached a similar color difference to sodium tripolyphosphate at its maximum allowed limit when applied at a concentration of 2% (w/w meat). Additionally, it was found that these hydrolysates obtained the same antioxidant activity as sodium tripolyphosphate, capturing free radicals at 10%. (4) Conclusion: The findings of this study suggest that bovine skin gelatin hydrolysates can be applied as an ingredient with functional properties, being an alternative to phosphates to improve the quality of meat products.

Automated method for the determination of total arsenic and selenium in natural and drinking water by HG-AAS.

A multicommutated flow system was designed and evaluated for the determination of total arsenic and selenium by Hydride Generation Atomic Absorption Spectrometry (HG-AAS). It was applied to the determination of arsenic and selenium in samples of natural and drinking water. Detection limits were 0.46 and 0.08 µg l(-1) for arsenic and selenium, respectively; sampling frequency was 120 samples h(-1) for arsenic and 160 samples h(-1) for selenium. Linear ranges found were 1.54-10 µg l(-1) (R = 0.999) for arsenic and 0.27-27 µg l(-1) (R = 0.999) for selenium. Accuracy was evaluated by spiking various water samples and using a reference material. Recoveries were in the range 95-116%. Analytical precision (s ( r ) (%), n = 10) was 6% for both elements. Compared with the Standard Methods, APHA, 3114B manual method, the system consumes at least 10 times less sample per determination, and the quantities of acid and reducing agent used are significantly lower with a reduction in the generation of pollutants and waste. As an additional advantage, the system is very fast, efficient and environmentally friendly for monitoring total arsenic and selenium levels in waters.

[Hepatitis B virus immunoglobulin on demand to prevent infection recurrence among liver allograft recipients: report of three cases]. / Trasplante hepático en cirrosis por virus B: profilaxis con gammaglobulina antiHBs en dosis a "demanda".

Infection recurrence rates among hepatitis B virus infected liver allograft recipients, may be as high as 80%. Immunoprophylaxis with anti HBVgammaglobulin may reduce these rates and improve survival. The dose of anti HBV gammaglobulin that must be used is not clearly defined. The most commonly accepted protocol uses 10,000 units during the anhepatic phase and 10,000 units daily during one week, followed by weekly doses of 10,000 units during one month and maintenance with 10,000 units monthly, without measuring anti hepatitis B surface antigen antibodies (antiHBs). Some reports recommend the use of immunoglobulin on demand, to maintain antiHBs titers between 100 and 250 U/l. The infection recurrence rates among patients treated with immunoglobulin and Lamivudine fluctuates between 0 and 10%, during follow up periods of 13 to 30 months. We report three liver allograft recipients that received immunoglobulin on demand, using a mean of 41,000 units, maintaining adequate antiHBs titers.

High-altitude is associated with better short-term survival in critically ill COVID-19 patients admitted to the ICU.

BACKGROUND: Multiple studies have attempted to elucidate the relationship between chronic hypoxia and SARS-CoV-2 infection. It seems that high-altitude is associated with lower COVID-19 related mortality and incidence rates; nevertheless, all the data came from observational studies, being this the first one looking into prospectively collected clinical data from severely ill patients residing at two significantly different altitudes. METHODS: A prospective cohort, a two-center study among COVID-19 confirmed adult patients admitted to a low (sea level) and high-altitude (2,850 m) ICU unit in Ecuador was conducted. Two hundred and thirty confirmed patients were enrolled from March 15th to July 15th, 2020. RESULTS: From 230 patients, 149 were men (64.8%) and 81 women (35.2%). The median age of all the patients was 60 years, and at least 105 (45.7%) of patients had at least one underlying comorbidity, including hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale (Score that estimates ICU mortality) at 72 hours was especially higher in the low altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the high-altitude group. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group. CONCLUSION: There has been a substantial improvement in survival amongst people admitted to the high-altitude ICU. Residing at high-altitudes was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours.

Bio-oxidation of H2S by Sulfolobus metallicus.

Sulfolobus metallicus is a hyperthermophilic and chemolithoautotrophic archaeon that uses elemental sulfur as an energy source. Its ability to oxidize H(2)S was measured either in the presence or absence of elemental sulphur, showing its ability for using both as an energy source. A biotrickling filter was set up and a biofilm of S. metallicus was established over the support. The maximum removal capacity of the biotrickling filter reached at 55°C was 40 g S/m(3)h for input loads higher than 70 g S/m(3)h. Thus, S. metallicus can be used in a biofiltration system for the treatment of waste gas emissions at high temperatures contaminated with H(2)S.

Differential regulation of TP73 isoforms by 1α,25-dihydroxyvitamin D3 and survivin in human colon and breast carcinomas.

We evaluate whether 1,25(OH)(2)D(3) downregulates TP73 variants in colon and breast carcinomas, the role of survivin in this context, and the significance of this network in the clinic. Tumor cells were treated/untreated with 1,25(OH)(2)D(3) and transiently transfected with survivin. Levels of survivin and TP73 variants were evaluated by quantitative RT-PCR and Western blotting. In 75 colon and 60 breast cancer patients, the expressions of survivin and TP73 isoforms were determined. Tumor characteristics were examined in each patient. Survivin protein levels were also evaluated in a subgroup of patients and cell lines. Decrease in survivin and TAp73 transcripts and protein and ΔNp73 mRNA was detected after 1,25(OH)(2)D(3) treatment. Ectopic survivin expression led to an increase in the TAp73, ΔNp73, ΔEx2p73, and ΔEx2-3p73 transcripts. In cancer patients, direct correlations were observed between TP73 variants and survivin levels. 1,25(OH)(2)D(3) negatively regulate survivin and TP73 variants in colon and breast cancer cells. Positive regulation of TP73 isoforms by survivin may exist, which reinforces the possibility that the downregulation of TP73 forms by 1,25(OH)(2)D(3) is survivin-dependent.