Cancer-associated fibroblasts in colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of mortality among cancers. Many aspects of this cancer are under investigation to find established markers of diagnosis, prognosis, and also potential drug targets. In this review article, we are going to discuss the possible solution to all these aims by investigating the literature about cancer-associated fibroblasts (CAFs) involved in CRC. Moreover, we are going to review their interaction with the tumor microenvironment (TME) and vitamin D and their role in tumorigenesis and metastasis. Moreover, we are going to expand more on some markers produced by them or related to them including FAP, a-SMA, CXCL12, TGF- β, POSTN, and β1-Integrin. Some signaling pathways related to CAFs are as follows: FAK, AKT, activin A, and YAP/TAZ. Some genes related to the CAFs which are found to be possible therapeutic targets include COL3A1, JAM3, AEBP1 and, CAF-derived TGFB3, WNT2, and WNT54.

Cancer-associated fibroblasts in colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of mortality among cancers. Many aspects of this cancer are under investigation to find established markers of diagnosis, prognosis, and also potential drug targets. In this review article, we are going to discuss the possible solution to all these aims by investigating the literature about cancer-associated fibroblasts (CAFs) involved in CRC. Moreover, we are going to review their interaction with the tumor microenvironment (TME) and vitamin D and their role in tumorigenesis and metastasis. Moreover, we are going to expand more on some markers produced by them or related to them including FAP, a-SMA, CXCL12, TGF- ß, POSTN, and ß1-Integrin. Some signaling pathways related to CAFs are as follows: FAK, AKT, activin A, and YAP/TAZ. Some genes related to the CAFs which are found to be possible therapeutic targets include COL3A1, JAM3, AEBP1 and, CAF-derived TGFB3, WNT2, and WNT54.

Analysis of partial azoospermia factor c deletion and DAZ copy number in azoospermia and severe oligozoospermia.

Microdeletions of the azoospermia factor (AZF) regions in the Y chromosome are a well-known genetic cause of male infertility, resulting in impairment of spermatogenesis. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. We investigated partial deletion of AZFc region and DAZ copy number in a population of Iranian infertile men and normozoospermic controls. In total, 154 infertile men (113 patients with azoospermia, 41 with oligozoospermia) and 111 normozoospermic controls were analysed using PCR. Gene dosage analysis of the DAZ genes was performed by fragment analysis. Our results showed that the frequencies of gr/gr deletion in the azoospermic, severe oligozoospermic and normozoospermic men were 4.4% (5/113), 7.3% (3/41) and 1.8% (2/111) respectively. In the azoospermic patients, the frequency of b2/b3 was 1.8% (2/113). Partial AZFc deletions were not significantly different between the infertile and normozoospermic men. The frequencies of gr/gr deletions and b2/b3 were not significantly different between the azoospermic/severe oligozoospermic men and normozoospermic controls. Our data suggested that gr/gr deletion was not associated with azoospermia/oligozoospermia in an Iranian population.

Influencing factors on the functional level of haemophilic patients assessed by FISH.

Joint destruction in early adulthood brings the patients to the orthopaedic clinics. If a haemophilic patient becomes disabled, it shows a number of factors such as timely diagnosis, availability of appropriate treatment depending on the country, access and affordability to treatments and equally importantly the responsibility of the patient in managing self care by remaining compliant by prescribed treatment regimen. We assessed the functional level by functional independence score in haemophilia (FISH). Overall, 104 patients with haemophilia A and 29 with haemophilia B were evaluated. We assessed the function of the patients by FISH. We divided the sum scores into weak (FISH score 8-16), moderate (17-24), and good (25-32). For evaluating the level of functional deficit in a 2 × 2 table, we categorized the weak and moderate levels into Disordered Group and the good level into Not-Disordered Group. The average age was 26.9 ± 14.24. Each 1 year increase in age can increase 1.07 fold the possibility of being placed in Disordered Function Group. Severe haemophilia can increase 7.34 fold, presence of inhibitor can increase 9.75 fold and home self-care increases 3.89 fold the possibility of being placed in Disordered Function Group. To decrease the burden of the cost on patient, family and the government, education plays the most important role. We suggest that we send a trained team of physician and nurses to the deprived villages and cities instead of waiting for the patient to refer to our Care Center.

High performances III-Nitride Quantum Dot infrared photodetector operating at room temperature.

In this paper we present a novel long wave length infrared quantum dot photodetector. A cubic shaped 6nm GaN quantum dot (QD) within a large 18 nm Al(0.2)Ga(0.8)N QD (capping layer) embedded in Al(0.8)Ga(0.2)N has been considered as the unit cell of the active layer of the device. Single band effective mass approximation has been applied in order to calculate the QD electronic structure. The temperature dependent behavior of the responsivity and dark current were presented and discussed for different applied electric fields. The capping layer has been proposed to improve upon the dark current of the detector. The proposed device has demonstrated exceptionally low dark current, therefore low noise, and high detectivity. Excellent specific detectivity (D*) up to approximately 3 x 10(8)CmHz(1/ 2)/W is achieved at room temperature.

A Y/15 translocation in a 45,X male with Prader-Willi syndrome.

We report a male neonate with a 45 X karyotype; the long arm of a chromosome 15 was translocated onto the proximal long arm of the Y chromosome. Breakpoints were identified by in situ fluorescence hybridization (FISH) on the proximal 15q13 and Yq11.2. The derivative chromosome has no primary centromere. Clinical features were compatible with Prader-Willi syndrome. This is the first report case ofmonosomy 15q and Yq deletion with Prader-Willi syndrome.

Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration.

BACKGROUND: Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1). METHOD: Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone. The animals were euthanized at 4 weeks postsurgery and block-biopsies of the defects were processed for histologic and histometric analysis. RESULTS: Surgical implantation of rhTGF-beta 1 resulted in minimal, if any, stimulation of alveolar bone or cementum regeneration. Linear bone and cementum regeneration in rhTGF-beta 1-treated defects was 1.2+/-0.6 and 0.01+0.01 mm, respectively. Corresponding values for the controls were 1.0+/-0.6 and 0.01+/-0.03 mm. CONCLUSIONS: The results suggest that, under the conditions (dose, carrier, defect type) evaluated here, treatment of periodontal defects in beagle dogs with rhTGF-beta 1 may be of limited clinical benefit.

Periodontal repair in dogs: effect of recombinant human transforming growth factor-beta1 on guided tissue regeneration.

This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor-beta1 (rhTGF-beta1) in conjunction with guided tissue regeneration (GTR). Supraalveolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-beta1, in a CaCO3/hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control). 20 microg of rhTGF-beta1 in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-beta1. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histometric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-beta1, to control defects, statistically significant differences were found for area (1.8+/-0.4 and 1.3+/-0.6 mm2, respectively; p<0.05) and density (0.3+/-0.1 and 0.2+/-0.03, respectively; p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinical model. Within the limitations of study, it may be concluded that rhTGF-beta1 has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.

The effect of urethral introducer tip catheters on the incidence of urinary tract infection outcomes in spinal cord injured patients.

PURPOSE: We attempted to determine whether an introducer tip catheter reduces urinary tract infection in spinal cord injured patients on intermittent catheterization. MATERIALS AND METHODS: The introducer tip catheter bypasses the colonized 1.5 cm. of the distal urethra. Enrolled patients were prospectively entered into the study in alternate groups depending on whether they reflex voided: group 1--on intermittent catheterization with the introducer tip catheter but not voiding spontaneously or wearing an external urinary catheter, group 2--same as group 1 but using a nonintroducer tip catheter; group 3--on intermittent catheterization with the introducer tip catheter, voiding by reflex and wearing an external urinary catheter, and group 4--same as group 3 but using a nonintroducer tip catheter. RESULTS: Statistical significance was shown when comparing patients using versus not using the introducer tip catheter regardless of whether an external urinary catheter was worn (p = 0.0121). A greater difference was noted between patients using and not using the introducer tip catheter in the intermittent catheterization only group (p = 0.0093). CONCLUSIONS: The introducer tip catheter decreased urinary tract infections in hospitalized men with spinal cord injury on intermittent catheterization.

Epidemiology of current treatment for sexual dysfunction in spinal cord injured men in the USA model spinal cord injury centers.

This study is a prospective multicenter cooperative survey of the evaluation and treatment of erectile dysfunction in men with spinal cord injury (SCI). Uniform database questionnaires were completed prospectively by patients seeking therapy for erectile dysfunction. Eighty-five SCI men aged 17-68 years (mean age = 26 +/- 17) were enrolled. Mean duration of traumatic SCI was 3 +/- 3.2 years (Range = 0.3-18 years). The level of injury was cervical in 20 patients, thoracic in 31, lumbar in 29 and sacral in five. Patients were fully evaluated and then counseled as to their therapeutic options. Twenty-eight chose to use a vacuum erection device (VED), 26 preferred pharmacological penile injection and five used both intracorporeal therapy and VED. The remainder were managed with marriage and sexual counseling in 10 patients, three underwent penile prosthesis placement and two used topical pharmacotherapy. Four patients used other forms of treatment and in nine no therapy was recommended. Of the patients that used pharmacologic injection only, 74 percent used papaverine as a single agent, 20 percent used papaverine with phentolamine, five percent used prostaglandin E (PGE1) alone and one percent used a mixture. Patients using injection therapy report sexual intercourse a mean of 3 +/- 3.4 times per month as compared with 5 +/- 3.2 times per month in those using VED. Five intracorporeal injection patients developed priapism while two patients using the VED developed subcutaneous bleeding and one developed penile ischemia. We conclude that although a spectrum of erectile dysfunction treatment is present among SCI centers, VED and pharmacological penile injection are by far the two most popular methods of treatment and papaverine is the most common drug. The incidence of complications is small in the model centers.

Selecting the appropriate urinary diversion procedure in the spinal cord injured: a poignant reminder.

Lower urinary tract reconstruction has been performed on the spinal injured population at our institution since 1988. Careful pre-operative evaluation including a detailed history, physical examination and radiographic and/or urodynamic studies are usually obtained to determine which type of procedure would be most beneficial for each individual patient. Typically, patients receive either a cutaneous (i.e., Kock or Indiana) diversion or undergo a form of bladder augmentation (usually ileocystoplasty). Pre-operative findings and the patient's history are carefully considered prior to choosing the appropriate procedure. Occasionally, a particular finding influences the decision. We describe a patient who received a hemi-Kock ileocystoplasty with a continent abdominal stoma who, in retrospect, would have benefitted from a supravesical diversion.

Fluorourodynamic and clinical evaluation in males following construction of a Kock ileal-urethral reservoir.

OBJECTIVES: Since 1986, we have offered the option of lower urinary tract reconstruction with the Kock ileal-urethral reservoir in selected male patients requiring diversion. This study provides insight into the functional characteristics of the Kock ileal-urethral reservoir and its effect on continence. METHODS: Twenty-four of the initial 225 male patients undergoing this procedure at our institution were evaluated by fluorourodynamics within 2 years of neobladder construction. Information regarding continence was also obtained by means of a patient interview and questionnaire. RESULTS: The average resting neobladder pressure was 8.5 cm H2O (range, 0 to 18). Reservoir capacity averaged 741 cc (range, 225 to 1400). Afferent nipple failure with bilateral grade II vesicoureteral reflux was noted in 1 patient (4%). Unsatisfactory daytime continence was seen in 2 patients (8%). Unsatisfactory nighttime continence was seen in 6 patients (25%). Patient satisfaction was high with an average rating of 8.6 on a scale of 1 to 10. CONCLUSIONS: Fluorourdynamic data demonstrate a low-pressure, high-capacity reservoir with a low incidence of reflux. The rate of continence is acceptable and patient satisfaction is excellent. The Kock ilealurethral reservoir is an excellent alternative to standard diversion for the male patient undergoing cystectomy.

Insulin and prostaglandins as signals between tumor and the host immune system.

The development of malignant tissue in vivo is partially favored by the immunosuppression that occurs in cancer patients. However, the signals between tumor and immune tissues remain to be identified. We present evidence that prostaglandins may act as one of these signals by a direct action on cells of the immune system, or by inhibition of insulin secretion which in turn suppresses immune function, or both.

Insulin and prostaglandins as signals between tumor and the host immune system

The development of malignant tissue in vivo is partially favored by the immunosuppression that occurs in cancer patients. However, the signals between tumor and immune tissues remain to be identified. We present evidence that prostaglandins may act as one of these signals by a direct action on cells of the immune system, or by inhibition of insulin secretion which in turn suppresses immune function, or both

Management of sphincter dyssynergia using the sphincter stent prosthesis in chronically catheterized SCI men.

This effort represents a subset analysis of the long-term Multicenter North American Trial of the UroLume sphincter stent prosthesis to determine the effect of the sphincter stent prosthesis in SCI men afflicted with detrusor-external sphincter dyssynergia (DESD) and chronically managed with an indwelling urinary catheter. Forty-one of 153 male patients in this study were evaluated urodynamically before and after placement of the sphincter stent prosthesis. Of the 41 patients, 34 (81 percent) suffered cervical-level injury while 10 patients (25 percent) had been treated previously with external sphincterotomy. Forty patients (98 percent) were troubled with recurrent urinary tract infections (UTI), with a mean of 4.6 +/- 3 episodes of UTI per year. Seven patients (17 percent) demonstrated hydronephrosis prior to stent placement. Follow-up ranged from six to 44 months. Voiding pressures decreased from a mean of 77 +/- 23 cmH2O preoperatively to 35 +/- 18 cmH2O at 12 months (n = 34) and 33 +/- 20 cmH2O at 24 months (n = 22) after stent insertion (p = 0.001). Post-void residual urinary volume decreased from 202 +/- 187 ml preinsertion to 64 +/- 69 ml at 24 months (p = 0.001) postinsertion. Maximum cystometric capacity remained constant at 201 +/- 144 ml preinsertion to 203 +/- 79 ml at 24 months (p = 0.75) postinsertion. No significant changes in any of the urodynamic parameters occurred after 24 months of follow-up between patients with (n = 10) and without (n = 31) previous external sphincterotomy. Neither hemorrhage requiring blood transfusion, obstructive hyperplastic epithelial overgrowth, stent encrustation or stone formation, nor soft tissue erosion occurred in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Utilization of rat and human sera to carry out incubation and perifusion of pancreatic islets.

Incubation of isolated pancreatic rat islets in a medium consisting of fresh rat or human sera and the measurement of insulin secretion after 60 min in the presence of 6.0-7.0 and 16.7 mM of glucose, were carried out. Perifusion experiments with isolated rat islets preincubated in the presence of rat or human sera and 0.2 mCi/mL of 45Ca2+ were also performed, and 45Ca2+ outflow rate and insulin secretion were analyzed. In both experiments, the usual islet responsiveness to glucose stimulation was preserved when compared with experiments in which Krebs-Henseleit (K-H) buffer was used as the medium. The results obtained demonstrate that both rat and human sera can be used as media for islets perifusion and incubation experiments, thus allowing for the effect(s) of circulating substances on insulin release to be examined.

Spectrophotometric determination of vanadium in different oxidation states with pyrogallol.

Determination of vanadium at low concentrations is easily performed with pyrogallol as a ligand which forms a bluish-violet complex with vanadium(III), (IV) or (V). The colour of the bluish-violet complex (lambda(max) = 580 nm) contrasts well with the colour of both pyrogallol and vanadium. The complexes are stable for several hours. Beer's law is obeyed over the range 0-14 mug/ml vanadium at pH 6. The apparent molar absorptivity at 580 nm is (7.75 +/- 0.25) x 10(3)1.mole(-1).cm(-1). The effects of diverse ions on the determination of vanadium have been fully studied. Only Mo(VI) and W(VI) interfere seriously. The method is selective, sensitive and can be applied to the determination of total vanadium in a variety of samples.

Studies on the corpuscles of Stannius of Botia lohachata.

The corpuscles of Stannius of Botia lohachata are made up of numerous large lobules, each of which is bounded by a septum and contains two types of cells. The secretory granules are PAS- and AF-positive, indicating that 1,2 glycol groups and non-sulphated mucoid substances are present. Detached cells in the lobule lumen are suggestive of holocrine secretion. The possibility of the existence of more than one secretory product is discussed.