Determining the optimal distal resection margin in rectal cancer patients by imaging of large pathological sections: An experimental study.

OBJECTIVE: To determine the distal resection margin in sphincter-sparing surgery in patients with low rectal cancer based on imaging of large pathological sections. METHODS: Patients who underwent sphincter-sparing surgery for ultralow rectal cancer at Guangxi Medical University Cancer Hospital within the period from January 2016 to March 2022 were tracked and observed. The clinical and pathological data of the patients were collected and analyzed. The EVOS fluorescence automatic cell imaging system was used for imaging large pathological sections. Follow-up patient data were acquired mainly by sending the patients letters and contacting them via phone calls, and during outpatient visits. RESULTS: A total of 46 patients (25 males, 21 females) aged 27 to 86 years participated in the present study. Regarding clinical staging, there were 9, 10, 16, and 10 cases with stages I, II, III, and IV low rectal cancer, respectively. The surgical time was 273.82 ±â€…111.51 minutes, the blood loss was 123.78 ±â€…150.91 mL, the postoperative exhaust time was 3.67 ±â€…1.85 days, and the postoperative discharge time was 10.36 ±â€…5.41 days. There were 8 patients with complications, including 3 cases of pulmonary infection, 2 cases of intestinal obstruction, one case of pleural effusion, and one case of stoma necrosis. The longest and shortest distal resection margins (distances between the cutting edges and the tumor edges) were 3 cm and 1 cm, respectively. The minimum length of the extension areas of the tumor lesions in the 46 images of large pathological sections was 0.1 mm, and the maximum length was 15 mm. Among the tumor lesions, 91.30% (42/46) had an extension area length of ≤5 mm, and 97.83% (45/46) had an extension area length of ≤10 mm. The length of the extension zone was not related to clinical pathological parameters (P > .05). CONCLUSION: In the vast majority of cases, the distal resection margin was at least 1 cm; thus, "No Evidence of Disease" could have been achieved. Additional high-powered randomized trials are needed to confirm the results of the present study.

Diuretics in Different Samples: Update on the Pretreatment and Analysis Techniques.

Diuretics are drugs that promote the excretion of water and electrolytes in the body and produce diuretic effects. Clinically, they are often used in the treatment of edema caused by various reasons and hypertension. In sports, diuretics are banned by the World Anti-Doping Agency (WADA). Therefore, in order to monitor blood drug concentration, identify drug quality and maintain the fairness of sports competition, accurate, rapid, highly selective and sensitive detection methods are essential. This review provides a comprehensive summary of the pretreatment and detection of diuretics in various samples since 2015. Commonly used techniques to extract diuretics include liquid-liquid extraction, liquid-phase microextraction, solid-phase extraction, solid-phase microextraction, among others. Determination methods include methods based on liquid chromatography, fluorescent spectroscopy, electrochemical sensor method, capillary electrophoresis and so on. The advantages and disadvantages of various pretreatment and analytical techniques are elaborated. In addition, future development prospects of these techniques are discussed.

HIGHLIGHTSPretreatment and determination methods of diuretics in diverse samples are reviewed.Applications of novel materials and technologies for SPE and sensors are highlighted.Pros and cons of recent pretreatment and analysis techniques used for diuretics are discussed.Applications of high-resolution mass spectrometry are described in detail.

Peptides derived from viral glycoprotein Gc Inhibit infection of severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel phlebovirus (SFTSV), characterized by fever, thrombocytopenia and leukocytopenia which lead to multiple organ failure with high mortality in severe cases. The SFTSV has spread rapidly in recent years and posed a serious threat to public health in endemic areas. However, specific antiviral therapeutics for SFTSV infection are rare. In this study, we demonstrated that two peptides, SGc1 and SGc8, derived from a hydrophobic region of the SFTSV glycoprotein Gc, could potently inhibit SFTSV replication in a dose-dependent manner without apparent cytotoxicity in various cell lines and with low immunogenicity and good stability. The IC50 (50% inhibition concentration) values for both peptides to inhibit 2 MOI of SFTSV infection were below 10 µM in L02, Vero and BHK21 cells. Mechanistically, SGc1 and SGc8 mainly inhibited viral entry at the early stage of the viral infection. Inhibition of SFTSV replication was specific by both peptides because no inhibitory effect was shown against other viruses including Zika virus and Enterovirus A71. Taken together, our results suggested that viral glycoprotein-derived SGc1 and SGc8 peptides have antiviral potential and warrant further assessment as an SFTSV-specific therapeutic.

Insight into the adsorption of europium(III) on muscovite and phlogopite: Effects of pH, electrolytes, humic substances and mica structures.

Europium(III), i.e., Eu(III), is chemically analogous to the trivalent lanthanides (Ln) and actinides (An). A good understanding of the adsorption behaviour of Eu(III) on mica group minerals is critical to the safety evaluation of the radioactive contamination. Nevertheless, the structural complexity of micaceous minerals makes it difficult to draw a consistent conclusion in the study of Eu(III) migration. In this work, we contrastively studied Eu(III) adsorption on dioctahedral muscovite and trioctahedral phlogopite as functions of pH, ionic strength, background electrolytes, interaction sequence, and fulvic acid (FA). Batch experiments showed that Eu(III) adsorption on both micas was strongly dependent on pH but quite independent on ionic strength that is determined by Na+. Planar sites are available on both muscovite and phlogopite while interlayer sites only on phlogopite under Na+ and Ca2+ electrolytes (not for K+ and Cs+). An interlayer expansion of phlogopite, as indicated by a newly appeared diffraction peak at ~6° 2-theta, occurred along with Eu(III) adsorption, which was also confirmed by transmission electron microscopy. Furthermore, the initial Eu(III) concentrations, the concentration ratios between Eu(III) and Cs+, and the reaction sequences of Eu(III)-electrolytes-FA affected both the adsorption behaviour of Eu(III) and reversely the structural alteration of phlogopite. The sequential extraction showed that the adsorbed Eu(III) was mainly in the ion-exchangeable form while the addition of FA could increase the portion of coordinative species. The currently proposed Eu(III) adsorption mechanism can shed new light on predicting the migration of Ln/An(III) at the mica-rich solid-liquid interface on a molecular scale.

Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71.

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 µM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

Comparative study of strontium adsorption on muscovite, biotite and phlogopite.

Micaceous minerals are the natural materials that can block radioactive strontium (Sr) released in the environment, and their adsorption capacity and mechanism are highly divergent owing to the different properties of micas. In this work, we comparatively studied the adsorption of Sr(II) on three typical micas, muscovite, biotite and phlogopite. The effects of pH, contact time, ionic strength, and background electrolyte were evaluated. It was found that phlogopite and muscovite had the largest solid-liquid distribution coefficient (Kd) for a reaction time of 48 h under acidic and alkaline conditions, respectively. Under alkaline conditions, as the reaction time increased to 44 days, phlogopite and muscovite showed the highest and lowest Kd, respectively. The Kd for Sr(II) adsorption on biotite and phlogopite increased with increasing pH but decreased with increasing pH for muscovite. X-ray diffraction analysis revealed that the interlayer weathering of phlogopite (a new diffraction peak appeared at 2-theta of ~6.1°) occurred along with the adsorption of Sr(II) below pH 9.0 under 0.01 mol/L NaCl. Furthermore, the adsorption of Sr(II) was significantly inhibited in the presence of 10-5 and 10-2 mol/L Cs+, resulting in similar adsorption capacity for phlogopite and muscovite at pH ~4.1. Consequently, the difference in Sr(II) adsorption on muscovite, biotite and phlogopite mainly came from the synergistic process of adsorption and weathering, which induced the differences in availability of interlayer sites among micas over a certain time.

Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis.

BACKGROUND: EGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance. METHODS: The expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test. RESULTS: HER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months). CONCLUSION: Our studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.

Modulation of pre-neoplastic biomarkers induced by sequential aflatoxin B1 and fumonisin B1 exposure in F344 rats treated with UPSN clay.

Populations consuming aflatoxin (AF) and fumonisin (FN)-contaminated foods may be at increased risk for hepatocellular carcinoma (HCC) and developmental disorders; consequently, development of intervention strategies to reduce AF/FN-induced liver disease and adverse health effects in humans could be very useful. Calcium montmorillonite clay (NovaSil) has been shown to absorb AF in vitro, in multiple animal models, as well as in human studies. In the present study, we aimed to evaluate whether uniform particle size NovaSil (UPSN) possessed an ability to modulate the co-carcinogenic potentials of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) in F344 rats. Sequential treatment of FB1 following AFB1 synergistically induces preneoplastic alterations as well as liver damage, indicating that AFB1 acts as an initiator while FB1 as a promoter in the carcinogenesis model, confirming findings from previous studies. The enterosorbent agent UPSN clay at dose of up to 0.5% in diet was shown to be effective in modulating the toxicity and carcinogenicity of co-exposure to AFB1 and FB1, as demonstrated by significant reduction in number and size of hepatic GST-P+ foci, in alterations indicative of liver toxicity, and in levels of AFB1 and FB1 biomarkers.

Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell activation and Klebsiella pneumonia liver translocation.

Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The effect and mechanism of diabetes on KP liver abscess was examined in streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP translocation to liver and plasma alaine transaminase levels were increased and liver clearance of KP was decreased in DM mice. Diabetic mice exhibited overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas growth in intestine, increased intestinal iNOS protein and nitrite levels in portal vein, and increased IL-1ß and TNF-α expression of Kupffer cells. Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation reversed diabetes-induced enteric dysbiosis, NO levels in portal vein, and KP translocation to liver. L-NAME treatment decreased intestinal iNOS protein expression as well as Kupffer cell activation and increased liver clearance of KP in DM mice. Dead E.coli (2×108 CFU/ml) feeding for one week induced iNOS and TLR4 expression of intestine in germ-free (GF) mice. Dead bacteria feeding induced IL-1ß and TNF-α expression of Kupffer cells in GF mice but not in GF TLR4-/- mice. In conclusion, balance of intestinal microflora is important for preventing intestinal iNOS expression, Kupffer cell activation, and KP liver translocation in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L. salivarius decreases diabetes-induced intestinal iNOS expression and KP liver translocation. Diabetes induces Kupffer cell activation and KP liver translocation through enteric dysbiosis and nitric oxide production.

Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction.

Dietary co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) and their interaction on hepatocellular carcinogenesis is of particular concern in toxicology and public health. In this study we evaluated the liver preneoplastic effects of single and sequential dietary exposure to AFB1 and FB1 in the F344 rat carcinogenesis model. Serum biochemical alterations, liver histopathological changes, and the formation of liver glutathione S transferase positive (GST-P+) foci were the major outcome parameters examined. Compared to the AFB1-only treatment, the FB1-only treatment induced less dysplasia, and more apoptosis and mitoses. Sequential AFB1 and FB1 treatment lead to increased numbers of dysplasia, apoptosis and foci of altered hepatocytes, as compared to either mycotoxin treatment alone. More importantly, sequential exposure to AFB1 and FB1 synergistically increased the numbers of liver GTP-P+ foci by approximately 7.3-and 12.9-fold and increased the mean sizes of GST-P+ foci by 6- and 7.5-fold, respectively, as compared to AFB1- or FB1-only treatment groups. In addition, liver ALT and AST levels were significantly increased after sequential treatment as compared to single treatment groups. The results demonstrate the interactive effect of dietary AFB1 and FB1 in inducing liver GST-P+ foci formation and provide information to model future intervention studies.

Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P < 0.05). Our result suggested that pretreatment status of TP and HIF-1α were found to predict pathologic response and outcomes in clinical stage II/III rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

Prognostic factors of hepatocellular carcinoma patients treated by transarterial chemoembolization.

We aim to investigate the clinical characteristics and prognostic factors of Hepatocellular Carcinoma (HCC) patients treated by transarterial chemoembolization (TACE) in Chinese cohort. A total of 2,493 HCC patients treated by TACE were included in this retrospective study. Patients were divided into the younger group (n=1,877) or the elderly group (n=616) based upon their ages (cut-off value of 60 y/o). Chi-square test or Wilcoxon rank-sum test was used to compare patients' characteristics. Univariate and multivariate analysis were used to determine prognostic factors. When compared with the younger group, the elderly group had lower male/female ratio and family liver disease history ratio, as well as advanced stage or Child-Pugh grade B patients. The median survival time was 8 months and 27 months for the younger and the elderly group, respectively. The 1-, 2-, and 3-year survival rates in the younger group and the elderly group were 31.82%, 12.5%, 6.53%, and 84.66%, 53.28%, 28.39%, respectively. Multivariate analysis showed that HBV infection, AFP value, TNM stage, Child-Pugh class, portal vein tumor thrombus (PVTT) and tumor number were independent prognostic factors for the younger patients; the elderly ones had similar independent prognostic factors except for HBV infection. The elderly group had lower male/female ratio and family history ratio, as well as advanced stage or Child-Pugh grade B patients. The elderly seems to have better prognosis than the younger ones, which is probably related to the fact that the elderly have lower tumor burden and better liver function.

Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin.

Aflatoxins (AFs) and fumonisins (FBs) can co-contaminate foodstuffs and have been associated with hepatocellular and esophageal carcinomas in humans at high risk for exposure. One strategy to reduce exposure (and toxicity) from contaminated foodstuffs is the dietary inclusion of a montmorillonite clay (UPSN) that binds AFs and FBs in the gastrointestinal tract. In this study, the binding capacity of UPSN was evaluated for AFB1, FB1 and a combination thereof in Fischer 344 rats. Rats were pre-treated with different dietary levels of UPSN (0.25% or 2%) for 1 week. Rats were gavaged with a single dose of either 0.125 mg AFB1 or 25 mg FB1 per kg body weight and a combination thereof in the presence and absence of an aqueous solution of UPSN. The kinetics of mycotoxin excretion were monitored by analyzing serum AFB1 -albumin, urinary AF (AFM1) and FB1 biomarkers over a period of 72 h. UPSN decreased AFM1 excretion by 88-97%, indicating highly effective binding. FB1 excretion was reduced, to a lesser extent, ranging from 45% to 85%. When in combination, both AFB1 and FB1 binding occurred, but capacity was decreased by almost half. In the absence of UPSN, the combined AFB1 and FB1 treatment decreased the urinary biomarkers by 67% and 45% respectively, but increased levels of AFB1 -albumin, presumably by modulating its cytochrome metabolism. UPSN significantly reduced bioavailability of both AFB1 and FB1 when in combination; suggesting that it can be utilized to reduce levels below their respective thresholds for affecting adverse biological effects.

Development of a questionnaire on everyday navigational ability to assess topographical disorientation in Alzheimer's disease.

We developed a Questionnaire on Everyday Navigational Ability (QuENA) to detect topographical disorientation (TD) in patients with Alzheimer's disease (PwAD). In the QuENA, 3 items were designed to assess landmark agnosia, 2 for egocentric disorientation, 3 for heading disorientation, and 2 for inattention. The PwAD and their caregivers rated QuENA according to which TD symptoms would occur. Regarding the construct validity, confirmatory factor analysis showed that the caregiver version of the QuENA fits the proposed TD model well but the patient version does not. Regarding the internal consistency, the Cronbach's α for the caregiver version was 0.91 and that for the patient version was 0.87. A discrepancy existed between the appraisal of navigational abilities by PwAD and by caregivers, and it was correlated with the number of getting lost (GL) events. The caregiver version of QuENA is a feasible, reliable, and valid instrument to assess TD and it also discriminates well between the PwAD with GL and those without.

Visualized analysis of mixed numeric and categorical data via extended self-organizing map.

Many real-world datasets are of mixed types, having numeric and categorical attributes. Even though difficult, analyzing mixed-type datasets is important. In this paper, we propose an extended self-organizing map (SOM), called MixSOM, which utilizes a data structure distance hierarchy to facilitate the handling of numeric and categorical values in a direct, unified manner. Moreover, the extended model regularizes the prototype distance between neighboring neurons in proportion to their map distance so that structures of the clusters can be portrayed better on the map. Extensive experiments on several synthetic and real-world datasets are conducted to demonstrate the capability of the model and to compare MixSOM with several existing models including Kohonen's SOM, the generalized SOM and visualization-induced SOM. The results show that MixSOM is superior to the other models in reflecting the structure of the mixed-type data and facilitates further analysis of the data such as exploration at various levels of granularity.

The occipital white matter lesions in Alzheimer's disease patients with visual hallucinations.

PURPOSE: Investigators have suggested that lesions responsible for visual hallucinations (VHs) are situated in the visual association cortex. The aim of this study was to assess the relationship between occipital white matter lesions and VHs in Alzheimer's disease (AD) patients. METHODS: AD patients with a history of VHs (AD+VH) and those without (AD-VH) were retrospectively studied. The two groups of patients were matched by sex and mental state. All subjects underwent brain magnetic resonance image (MRI) scans. The periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWHs) on MRIs were rated by two raters using a semiquantitative scoring method (0=absent; 6=confluent). RESULTS: Five AD+VH patients and five AD-VH patients were enrolled into this study. The occipital PVH score was higher in the AD+VH patients than in the AD-VH patients. The occipital DWH score was zero in both groups. CONCLUSION: The presence of VHs in AD was associated with increased occipital PVHs and an absence of occipital DWHs on brain MRIs, implying that structural lesions in the geniculocalcarine region and preserved subcortical connections with visual association areas are involved in the genesis of VHs in AD.

Temporal patterns of body temperatures in the acute stage of stroke.

OBJECTIVE: The present study aimed to describe the day-by-day temporal patterns of body temperatures in acute stroke and to delineate the differences in serial daily changes in body temperatures between intracerebral hemorrhage (ICH) and cerebral infarct (CI). METHODS: We retrospectively enrolled 90 patients (32 with ICH and 58 with CI), admitted within 12 hours after the onset of stroke. Body temperatures were measured as the tympanic temperatures during the initial 6 days of hospitalization. Patients with clinical infections were excluded. The severity of stroke was assessed by Scandinavian Stroke Scale (SSS). SSS score < or = 30 was defined as severe stroke, and SSS score >30 as mild-to-moderate stroke. RESULTS: Mean body temperature was significantly higher in patients with ICH than those with CI in 0 approximately 12 hours; 12 approximately 24 hours, 24 approximately 48 hours, and 48 approximately 72 hours (all p<0.05) after the onset of stroke. Among patients with ICH, the body temperature was significantly higher in the severe group than the mild-to-moderate group during 24 approximately 48 hours and 48 approximately 72 hours (both p<0.05) after the onset of stroke. No significant difference in body temperatures was observed between patients with severe stroke and patient with mild-to-moderate CI. CONCLUSIONS: The serial time course of body temperature in the acute stage of stroke differs between ICH and CI. This study showed that, in ICH but not in CI, the elevation of body temperature has significant association with the stroke severity. Our results may help in the management of hyperthermia during acute stroke.

Rigidity of collagen fibrils controls collagen gel-induced down-regulation of focal adhesion complex proteins mediated by alpha2beta1 integrin.

Previous studies have shown that collagen gel overlay induced selective proteolysis of focal adhesion complex proteins in Madin-Darby canine kidney (MDCK) cells. In this study, we examined whether morphological and biochemical changes were present in cells cultured on collagen gel. We found that focal adhesion complex proteins, including focal adhesion kinase (FAK), talin, paxillin, and p130cas, but not vinculin, were decreased within 1 h when MDCK cells were cultured on collagen gel. Collagen gel-induced selective decrease of focal adhesion proteins was observed in all lines of cells examined, including epithelial, fibroblastic, and cancer cells. Matrigel also induced selective down-regulation of focal adhesion proteins. However, cells cultured on collagen gel- or matrigel-coated dishes did not show any changes of focal adhesion proteins. These data suggest that the physical nature of the gel, i.e. the rigidity, is involved in the expression of focal adhesion proteins. The collagen gel-induced down-regulation of focal adhesion complex proteins was caused by reduction of protein synthesis and activation of proteases such as calpain. Overexpression of a dominant negative mutant of discoidin domain receptor 1 (DDR1) or FAK-related non-kinase (FRNK) did not prevent collagen gel-induced down-regulation of the focal adhesion complex protein, whereas an anti-alpha2beta1 integrin-neutralizing antibody completely blocked it. Taken together, our results indicate that the rigidity of collagen gel controls the expression of focal adhesion complex proteins, which is mediated by alpha2beta1 integrin but not DDR1.