Extraordinary Response of Metastatic Pancreatic Cancer to Chemotherapy / 대한소화기암학회지

A 58-year-old woman presented with right flank and back pain for one month. After undergoing an abdominal computed tomography (CT), she was referred to our hospital. The abdominal CT showed a hypodense pancreatic tail mass with multiple retroperitoneal lymph node metastases. Positron emission tomography-computed tomography (PET-CT) scan showed high 18F-FDG uptake in pancreatic tumor and enlarged lymph nodes. Endoscopic ultrasound fine needle aspiration (EUS-FNA) revealed adenocarcinoma, which stained strongly in hENT1 (human equilibrative nucleoside transporter 1) on immunohistochemistry. She received gemcitabine 1,000 mg/m² + nanoparticle albumin-bound paclitaxel 125 mg/m² as a palliative chemotherapy. Follow-up abdominal CT and PET-CT after 4 cycles of chemotherapy showed that both pancreatic mass and the metastatic retroperitoneal lymph nodes were nearly disappeared. We report a case of 58-year-old female with metastatic pancreatic cancer who had a dramatic response to palliative chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel).

Síndrome H: primer caso pediátrico reportado en América Latina / H syndrome: First reported paediatric case in Latin America

Introducción: El síndrome H es una enfermedad genética extremadamente rara de compromiso multisistémico, el cual clínicamente puede ser reconocido de forma precoz, ofreciendo de manera oportuna un seguimiento, tratamiento específico y asesoramiento genético. Objetivo: Presentar un caso con características «típicas del síndrome H¼ para favorecer su identificación precoz. Caso clínico: Varón de 8 años de edad, evaluado por tumoraciones testiculares, lesiones dérmicas tipo hiperpigmentación con hipertricosis, retraso del lenguaje, talla baja, deformidades articulares, hipoacusia neurosensorial bilateral, anemia, hipergammaglobulinemia y alteraciones óseas. En los estudios histológicos de la piel y las masas testiculares se observó infiltración linfoplasmocitaria. El secuenciamiento del gen SLC29A3 detectó una mutación homocigota c.1087 C>T (p.Arg363Trp; rs387907067) concluyente con el síndrome H, la cual ha sido reportada previamente. Conclusiones: Este es el primer caso reportado en Latinoamérica del síndrome H, cuyas características descritas son parte del espectro clínico. El hallazgo clínico principal, que orienta al diagnóstico, es la hiperpigmentación acompañada de hipertricosis.

Introduction: H Syndrome is an extremely rare genetic disease, with a multisystemic character and which can be identified in early childhood, offering the opportunity of specific treatment and genetic counselling. Objective: To present a clinical case with "typical" characteristics of H Syndrome. Clinical case: The case is presented of an 8-year-old male patient who presented with testicular tumours and skin lesions characterised by hyperpigmentation with hypertrichosis, language delay, short stature, and joint deformities. He also presented with bilateral sensorineural hearing loss, anaemia, hypergammaglobulinaemia, and bone disorders. Histopathology studies of the skin and testicular masses reported lymphoplasmacytic infiltration. Sequencing analysis of gene SLC29A3 showed the homozygote mutation c.1087 C>T (p.Arg363Trp; rs387907067). Conclusions: These findings are consistent with H syndrome, and this is the first reported case in Latin America. The key to the diagnosis is the finding of hyperpigmentation with hypertrichosis.

Identification of a novel mutation in solute carrier family 29, member 3 in a Chinese patient with H syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>H syndrome (OMIM 612391) is a recently described autosomal recessive genodermatosis characterized by indurated hyperpigmented and hypertrichotic skin, as well as other systemic manifestations. Most of the cases occurred in the Middle East areas or nearby countries such as Spain or India. The syndrome is caused by mutations in solute carrier family 29, member 3 (SLC29A3), the gene encoding equilibrative nucleoside transporter 3. The aim of this study was to identify pathogenic SLC29A3 mutations in a Chinese patient clinically diagnosed with H syndrome.</p><p><b>METHODS</b>Peripheral blood samples were collected from the patient and his parents. Genomic DNA was isolated by the standard method. All six SLC29A3 exons and their flanking intronic sequences were polymerase chain reaction (PCR)-amplified and the PCR products were subjected to direct sequencing.</p><p><b>RESULTS</b>The patient, an 18-year-old man born to a nonconsanguineous Chinese couple, had more extensive cutaneous lesions, involving both buttocks and knee. In his genomic DNA, we identified a novel homozygous insertion-deletion, c. 1269_1270delinsA, in SLC29A3. Both of his parents were carriers of the mutation.</p><p><b>CONCLUSIONS</b>We have identified a pathogenic mutation in a Chinese patient with H syndrome.</p>

Relationship between single nucleotide polymorphism of the equilibrative nucleoside transporter ENT3 and susceptibility to lung cancer / 中国肺癌杂志

<p><b>BACKGROUND AND OBJECTIVE</b>The transport of nucleoside transmembrane mediated by equilibrative nucleoside transporter (ENT) plays an important role in regulating various cellular functions, and the ENT gene may be candidate gene of tumors. The aim of this study is to investigate the association between the single nudcleotide polymorphism (SNP) of ENT3 and the hereditary susceptibility of lung cancer.</p><p><b>METHODS</b>A case-control study was performed involved in 351 lung cancer patients and 207 cancer-free controls from Chinese population in Shanghai pulmonary hospital. The rs10999776 (C>T) polymorphism was determined by using Real-time PCR with AllGlo probes. The frequency distribution of genotypes and allele between lung cancer and controls groups was analyzed by chi-square test. The association between polymorphism in the ENT3 gene with the risk of lung cancer was estimated by computing odds ration (OR) and 95%CI.</p><p><b>RESULTS</b>The genotype (CC, TC, IT) and allele distribution of the ENT3 SNP in the patients with lung cancer was not significantly different compared with that in controls (P > 0.05). Compared with never-smokers with wild homozygous genotype, smokers with T allele (TC+TT) had increased risk of lung cancer (OR = 2.848, 95% CI: 1.536-4.879, P = 0.005), and those with pack-years of smoking more than 30 had higher risk (OR = 3.076, 95% CI: 2.308-6.741, P = 0.001). And the risk of squamous cell carcinoma significantly increased in smokers, especially those with T allele (TC+TI) genotype (OR = 6.066, 95% CI: 2.884-12.758, P < 0.001). The genotype with smoking conditions had no significant effect on adenocarcinoma (all P > 0.05).</p><p><b>CONCLUSION</b>The results suggested rs10999776 polymorphism may implicate in the risk of squamous cell carcinoma in Chinese population which may interact with smoking-exposure.</p>

Abstracts of award-winning posters, 14th annual health sciences poster conference, Faculty of medicine, Health Sciences Centre, Kuwait University, Kuwait, April 21-23, 2009

It has been shown in the rat that insulin affects expression of the rat equilibrative nucleoside transporter [rENT] 2 and rat concentrative nucleoside transporter [rCNT] 1 and 2 in cardiac fibroblasts and adenosine uptake by cardiac myocytes. The aim of this study was to explore the effects of streptozotocin [STZ]-induced diabetes in the rat heart on the expression of rENTl and 2 and rCNTl, 2 and 3. Diabetes was induced in Sprague-Dawley rats by an i.p. injection of STZ [60 mg/kg]; controls were treated with vehicle. Diabetes was confirmed by plasma glucose >17 mM. Rats were sacrificed after 4 weeks, and cardiac muscle samples were frozen in liquid N[2]. Real-time PCR was used to estimate the threshold cycles for target amplification [Ct] values. The differences between the Ct values for ENTs and CNTs and the Ct values for the housekeeping gene [3-actin were calculated [Act], and the difference between diabetic and control rats was tested for significance. Data are presented as mean +/- SD from 3 samples. Results: The Ct value of [3-actin did not differ significantly between the groups [p > 0. 05], so this gene was used as the endogenous control. In the control group, the mRNA for rCNT2, rENT2, rENTl and rCNTl were detected with the Act 2.4 +/- 0.4, 4. 3 +/- 0.3, 7.4 +/- 0.6 and 8.1 +/- 0.1, respectively. The mRNA for rCNT3 was apparently absent. Four-week diabetes caused a significant decrease in the amount of mRNA for rCNTl [p < 0.05 vs. control], while the amount of mRNA for other transporters did not change significantly. The observed changes in the amount of rCNTl mRNA may indicate a decrease in the amount of this pyrimidine-selective transporter in the membrane, which in turn could reduce the cellular uptake of py-rimidines in diabetes

Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway

Although the apoptosis of chondrocytes plays an important role in endochondral ossification, its mechanism has not been elucidated. In this study, we show that guanosine induces chondrocyte apoptosis based on the results of acridine orange/ ethidium bromide staining, caspase-3 activation, and sub-G1 fraction analysis. The potent inhibitory effect of dipyridamole, a nucleoside transporter blocker, indicates that extracellular guanosine must enter the chondrocytes to induce apoptosis. We found that guanosine promotes Fas-Fas ligand interaction which, in turn, leads to chondrocyte apoptosis. These findings indicate a novel mechanism for endochondral ossification via metabolic regulation.