Pelvic infection caused by periodontitis: A case report.

Oral bacteria in patients with periodontitis can disseminate into the bloodstream via broken oral epithelial cells, causing odontogenic maxillofacial infections, brain abscesses and endocarditis. However, pelvic infection caused by periodontitis is rare. The case of a 48-year-old woman with a long history of recurrent periodontal infections, who complained of abdominal distention and pain for 14 days after dental implantation, is reported here. Pelvic ultrasound and magnetic resonance imaging signaled multiple inflammatory encapsulated effusions in the posterior uterus, which were removed by laparoscopic surgery and tested with metagenomic next-generation sequencing (mNGS). Through mNGS, numerous oral pathogens, including Filifactor alocis, were identified in the pelvic effusions. The patient was subsequently diagnosed with a pelvic infection originating from periodontitis, and recovered after undergoing surgery and targeted antibacterial treatment. Thus, the possibility of extrabuccal complications in patients with a history of periodontitis or invasive oral procedures merits closer attention.

The Novel Use of IL-28 as an Effective Radiosensitizer in Pancreatic Cancer.

BACKGROUND/AIM: Pancreatic cancer is the second most common gastrointestinal cancer in the world, yet the five-year survival outcome rate of less than 5% urges for improvement in medical interventions of pancreatic cancer. Currently, high dose radiation therapy (RT) is used as an adjuvant treatment; however, the high level of RT required to treat advanced neoplasms leads to high incidence rates of side effects. In recent years, the utilization of cytokines as radiosensitizing agents has been studied, in order to reduce the amount of radiation required. However, few studies have examined IL-28 regarding its potential as a radiosensitizer. This study is the first to utilize IL-28 as a radiosensitizing agent in pancreatic cancer. MATERIALS AND METHODS: MiaPaCa-2, a widely used pancreatic cancer cell line was used in this study. Clonogenic survival and cell proliferation assays were used to evaluate growth and proliferation of MiaPaCa-2 cells. Caspase-3 activity assay was used to evaluate apoptosis of MiaPaCa-2 cells and RT-PCR was used to study the possible molecular mechanisms. RESULTS: Our results showed that IL-28/RT enhanced RT-induced inhibition of cell proliferation and promoted apoptosis of MiaPaCa-2 cells. Furthermore, compared to RT alone, we found that IL-28/RT up-regulated the mRNA expression of TRAILR1 and P21, while down-regulating mRNA expression of P18 and survivin in MiaPaCa-2 cells. CONCLUSION: IL-28 has the potential to be used as a radiosensitizer for pancreatic cancer and warrants further investigation.

Hernia uterine inguinale associated with Mayer-Rokitansky-Küster-Hauser syndrome: Three case reports and literature review.

RATIONALE: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome) present with genital inguinal hernia was rare and probably under reported, on account of lack in typical gynecological symptom. It should be regarded with care.Here 3 cases diagnosed at our institution with detailed clinical information were present, and the literature was reviewed to paint a comprehensive profile of hernia uterine inguinale associated with MRKH syndrome. PATIENT CONCERNS: Case no. 1 was a 36-year-old female with recurrent dragalgia for 5 years. Left rudimentary uterus at the left groin area was revealed by sonography scan and confirmed by diagnostic laparoscopy.Case no. 2 was a 27-year-old woman diagnosed with MRKH syndrome and her MRI examination suggested a suspicious swelling measuring 2.0cm×2.0cm in left groin. The left nonfunctionally rudimentary uterus and adnexa were incarcerated in the left inguinal hernial sac, which was revealed by laparoscopy.Case no. 3 was a 29-year-old woman, admitted with right abdominal pain with a provisional diagnosis of appendicitis. After appendicectomy, pelvic exploration showed a part of left rudimentary uterus and elongated oviduct herniated through the left internal inguinal ring. DIAGNOSES: Hernia uterine inguinale associated with MRKH syndrome. INTERVENTIONS AND OUTCOMES: Case no.1: When the rudimentary uterus was pulled out from the hernia sac, it appearance dark ocher. Then the left rudimentary uterus was removed and the indirect defect of inguinal duct was closed.The patient was followed up for 18 months with no recurrence of abdominal pain.Case no.2 and 3:The left rudimentary uterus were replaced from the hernia sac, and the indirect defect was fixed with sutures.The patients recovered smoothly without complications for 12-month follow-up. LESSONS: Left involvement of rudimentary uterus was frequently observed in patients with MRKH syndrome, along with ipsilateral ovary and/or fallopian tube horned in the hernia. Abdominal pain or inguinale mass could be the chief complaints while some individuals were asymptomatic. Either surgical removal or replacement of rudimentary uterus was an effectively optional treatment strategy for hernia uterine inguinale.When a patient with MRKH syndrome presented with abdominal pain of unknown cause or inguinal mass, rudimentary uterine inguinal hernia should be suspected.

Functional characteristics of a broad spectrum of TBX6 variants in Mayer-Rokitansky-Küster-Hauser syndrome.

PURPOSE: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in females. Whole-gene deletion and loss-of-function variants in TBX6 have been identified in association with MRKHS. We aimed to expand the spectrum of TBX6 variants in MRKHS and explore the biological effect of the variant alleles. METHODS: Rare variants in TBX6 were called from a combined multiethnic cohort of 622 probands with MRKHS who underwent exome sequencing or genome sequencing. Multiple in vitro functional experiments were performed, including messenger RNA analysis, western blotting, transcriptional activity assay, and immunofluorescence staining. RESULTS: We identified 16 rare variants in TBX6 from the combined cohort, including 1 protein-truncating variant reported in our previous study and 15 variants with unknown effects. By comparing the prevalence of TBX6 variants in the Chinese MRKHS cohort vs 1038 female controls, we observed a significant mutational burden of TBX6 in affected individuals (P = .0004, odds ratio = 5.25), suggesting a causal role of TBX6 variants in MRKHS. Of the 15 variants with uncertain effects, 7 were shown to induce a loss-of-function effect through various mechanisms. The c.423G>A (p.Leu141=) and c.839+5G>A variants impaired the normal splicing of TBX6 messenger RNA, c.422T>C (p.Leu141Pro) and c.745G>A (p.Val249Met) led to decreased protein expression, c.10C>T (p.Pro4Ser) and c.400G>A (p.Glu134Lys) resulted in perturbed transcriptional activity, and c.356G>A (p.Arg119His) caused protein mislocalization. We observed incomplete penetrance and variable expressivity in families carrying deleterious variants, which indicates a more complex genetic mechanism than classical Mendelian inheritance. CONCLUSION: Our study expands the mutational spectrum of TBX6 in MRKHS and delineates the molecular pathogenesis of TBX6 variants, supporting the association between deleterious variants in TBX6 and MRKHS.

A genotype-first analysis in a cohort of Mullerian anomaly.

Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct. M.A. can either be isolated or be involved in Mendelian syndromes, such as Dandy-Walker syndrome, Holt-Oram syndrome and Bardet-Biedl syndrome, which are often associated with both uterus and kidney malformations. In this study, we applied a genotype-first approach to analyze the whole-exome sequencing data of 492 patients with M.A. Six potential pathogenic variants were found in five genes previously related to female urogenital deformities (PKD1, SON, SALL1, BMPR1B, ITGA8), which are partially overlapping with our patients' phenotypes. We further identified eight incidental findings in seven genes related to Mendelian syndromes without known association with reproductive anomalies (TEK, COL11A1, ANKRD11, LEMD3, DLG5, SPTB, BMP2), which represent potential phenotype expansions of these genes.

Raspberry Extract With Potential Antitumor Activity Against Cervical Cancer.

BACKGROUND: Cervical cancer (CC) is one of the leading causes of mortality worldwide. Previously, we reported that blueberry extract constrains the growth of CC. Raspberry is a widely consumed fruit that exhibits antitumor properties against several cancer types but little is known about its direct effect on CC. This study was designed to investigate the potential antitumor effect of raspberry extract (RE) on CC cells and to elucidate the possible mechanisms behind it. MATERIALS AND METHODS: Clonogenic survival assay and caspase-3 activity kits were used to evaluate the effects of RE on cell survival, proliferation, and apoptosis of a widely used CC cell line, HeLa. Possible molecular mechanisms were investigated using reverse transcription-polymerase chain reaction. RESULTS: The percentage of colonies and optic density value of HeLa cells decreased in the presence of RE in comparison to controls. Relative caspase-3 activity in cancer cells increased in the presence of RE in comparison to controls. The antitumor effect displayed on HeLa cells by RE was associated with the increased expression of antiproliferative molecule P53 and the increased expression of pro-apoptotic molecule tumor necrosis factor receptor superfamily member 6 (FAS). CONCLUSION: RE displays anticancer activity against CC HeLa cells. The mechanism behind this is by up-regulation of anti-proliferative molecule P53 and pro-apoptotic molecule FAS.

Laparoscopic uterovaginal anastomosis in patients with congenital cervicovaginal atresia: An institutional experience with 23 patients.

OBJECTIVE: To introduce our experience of laparoscopic uterovaginal anastomosis and operative outcomes following this technique and update the clinical management of congenital cervicovaginal atresia. STUDY DESIGN: Between March 2015 and January 2019, twenty-three patients with congenital cervicovaginal atresia underwent laparoscopic uterovaginal anastomosis and Luohu procedure. Their clinical characteristics, surgical outcomes and follow-up data were retrospectively reviewed. RESULTS: The mean ± SD age of the cases was 16.4 ± 4.0 (11-26) years. All patients had a history of primary amenorrhea and cyclical abdominal pain, and the average delay in diagnosis from first symptoms was 33.5 ± 38 (1-156) months. Most of the patients had 1-3 cm long vaginal pouch. The operative procedure lasted 125 ± 32 (80-190) min. The average vaginal length at 1 month was 7.9 ± 1.3 (range 6-9) cm. All patients showed resumption of menstruation. The patients were followed for a mean of 27 ± 13 (12-56) months. During the follow-up, cervical stenosis did not occur in any of the cases. CONCLUSION: Laparoscopic uterovaginal anastomosis with Luohu procedure provided a minimally invasive, safe, and effective surgical option for the patients with congenital cervicovaginal atresia. The technique is uncomplicated, easy to learn and perform, and provides a functional and anatomic satisfactory result. No special surgical instruments are required with this technique.

Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.

Comparative study on life cycle assessment of gasoline with methyl tertiary-butyl ether and ethanol as additives.

China has proposed to use ethanol instead of methyl tert-butyl ether (MTBE) as a gasoline additive, with full compliance planned for 2020. At present, previous studies on gasoline additive focus almost exclusively on effects of fuel performance and engine, however, the environmental impact production and use of additives cannot be ignored. Herein, we use the life cycle assessment (LCA) method, the environmental effects of E10 (10% maize ethanol and 90% gasoline, v/v) and M10 (10% MTBE and 90% gasoline, v/v) were evaluated and compared. Quantifying the net environmental benefits of implementing this national policy from a life cycle perspective. The results showed that the environmental impact of E10 was 15.4% lower than that of M10. Thus, replacing MTBE with ethanol reduces the total environmental impact. However, there were some negative environmental impacts such as waste solids and water use. Finally, we propose further improvements to make E10 more environmentally friendly.

Detection of de novo genetic variants in Mayer-Rokitansky-Küster-Hauser syndrome by whole genome sequencing.

OBJECTIVE: The aim of this study was to use whole genome sequencing (WGS) help detect de novo mutations or pathogenic genes of Mayer-Rokitansky-Küster-Hauser syndrome type 1(MRKH syndrome type 1). STUDY DESIGN: This was a case-parent trios study. Nine unrelated probands, with MRKH syndrome type 1 and their parents were enrolled. The enrollment, sequencing process, establishment of the de novo mutations detecting procedure and experiment part were performed over a 2-year period. RESULTS: we detected 632 de novo single nucleotide variants (SNVs), 267 de novo small insertions/deletions (indels), 39 de novo structural variations (SVs) and 28 de novo copy number alterations (CNAs). Three novel damaging coding de novo SNVs with three damaging coding de novo genes (PIK3CD, SLC4A10 and TNK2) were revealed. Two SNVs were annotated of the promoter region of gene NBPF10 and 3'UTR of NOTCH2NL, potentially contributing to the pathogenesis of MRKH. CONCLUSION: We identified five de novo mutations in BAZ2B, KLHL18, PIK3CD, SLC4A10 and TNK2 by performing WGS, the functional involvement of all deleterious mutations in MRKH candidate genes of the trios warrant further study. WGS may complement conventional array to capture the complete landscape of the genome in MRKH.

Analysis of the artificial vaginal microecology in patients after laparoscopic peritoneal vaginoplasty.

To investigate the artificial vaginal microecological features in patients who underwent laparoscopic peritoneal vaginoplasty. 54 cases of patients with artificial vagina after laparoscopic peritoneal vaginoplasty were included in this study. Microecosystem evaluation was performed. Artificial vaginal functional tests and biopsy from vaginal walls were performed. After laparoscopic peritoneal vaginoplasty, the artificial vaginal flora intensity was level II∼III (88.9%); the vaginal flora diversity was level II∼III (72.2%); the predominant vaginal bacteria were gram-positive macrobacillus (27.8%); approximately 57.4% of the patients had vaginal pH ≤ 4.5; there was no pathogenic bateria or other pathogens; dysbiosis accounted for 53.7% of the patients (64.5% of the patients who had the vaginoplasty operation less than 2 years ago exhibited dysbiosis; 39.1% of the patients who had the operation at least 2 years ago exhibited dysbiosis). Vaginal dysbiosis is common after laparoscopic peritoneal vaginoplasty. However, as time goes by, the artificial vaginal microecological condition gradually becomes normal. Evaluation of vaginal microenvironment after laparoscopic peritoneal vaginoplasty might play an important role in reproductive tract infection prevention and neovagina health care.

Association between interleukin­33 and ovarian cancer.

Ovarian cancer is the leading cause of cancer­ associated mortality in the female reproductive system. Interleukin (IL)­33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL­33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL­33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL­33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase­3 activity kit were all used to evaluate the direct effects of IL­33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcription­polymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL­33; however, the relative caspase­3 activity in cancer cells was decreased in the presence of IL­33. Molecular mechanism studies revealed that the pro­proliferative effect of IL­33 on cancer cells was associated with decreased levels of p27, and the anti­apoptotic effect of IL­33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factor­related apoptosis­inducing ligand receptor 1 (TRAILR1). Therefore, IL­33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an anti­tumor effort in pancreatic cancer, the results of the present study indicated that IL­33 exhibited a significant onco­promoting effect on ovarian cancer. Accordingly, the inhibition of IL­33 may be a promising therapeutic strategy for ovarian cancer.

IL-33 notably inhibits the growth of colon cancer cells.

Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.

IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer.

IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.

The clinical application of laparoscope-assisted peritoneal vaginoplasty for the treatment of congenital absence of vagina.

OBJECTIVE: To evaluate the outcomes of laparoscope-assisted peritoneal vaginoplasty for the treatment of congenital vaginal atresia. METHODS: A retrospective study enrolled patients diagnosed with congenital vaginal atresia who were treated with one of two different laparoscope-assisted peritoneal vaginoplasty techniques (named Luohu-one and Luohu-two) between October 31, 2001 and December 31, 2014. Operative time, intraoperative bleeding volume, surgical difficulty, complications, and post-procedure sexual satisfaction were reported. RESULTS: Data were collected for 620 patients. The Luohu-one procedure was used in the treatment of 145 patients, while 475 patients were treated with the Luohu-two procedure. In 5 (0.8%) patients, it was necessary to perform a sigmoid colon vaginoplasty. During surgery, 16 patients experienced a rectal injury, among whom, 9 patients experienced a rectal-vaginal fistula. Follow-up data extending to 7years were available for 285 patients. Of these 285 patients, 231 agreed to report details of their sexual experiences. In total, 222 (96.1%) patients reported being very satisfied with their vaginal conditions and sex life. The Luohu-two procedure demonstrated shorter operative and recovery time, and reduced intraoperative bleeding. However, both procedures demonstrated satisfactory results. CONCLUSION: Laparoscope-assisted peritoneal vaginoplasty demonstrated good safety and effectiveness in the treatment of patients with congenital vaginal atresia.

IL-32α has differential effects on proliferation and apoptosis of human melanoma cell lines.

BACKGROUND: Interleukin-32 (IL-32) is a recently recognized intracellular, proinflammatory cytokine which may play a role in cancer metastasis and patient survival. The role of IL-32 in cancer, especially its direct effect on cancer cells, is not well understood. MATERIAL AND METHODS: Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining, and caspase-3 activity assay were used to investigate the in vitro role for IL-32α in human melanoma growth. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. RESULTS: Exogenous administration of IL-32α inhibited proliferation of the HTB-72 human melanoma cell line, but had little effect on other melanoma cell lines. Inhibition of proliferation in HTB-72 correlated with increased expression of p21 and p53. IL-32α administration also increased apoptosis in HTB-72. This finding correlated with increased expression of TRAILR1. CONCLUSIONS: The data presented suggest a direct effect of IL-32α on the growth of human melanoma and give some insight into the mechanisms which may in part govern this effect. J. Surg. Oncol. 2016;113:364-369. © 2016 Wiley Periodicals, Inc.

IL-9 inhibits HTB-72 melanoma cell growth through upregulation of p21 and TRAIL.

BACKGROUND: IL-9 is a pleiotropic cytokine produced mainly by Th9 cells. IL-9 may have an anti-proliferative role in murine melanoma, however, its effect on human melanoma is unknown. METHODS: We examined the effects of IL-9 on proliferation and apoptosis in four human melanoma cell lines, HTB-65, HTB-72, CRL-11147, and SK-Mel-5. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis, as appropriate. RESULTS: We found that IL-9 decreased the percentage of colonies of HTB-72 and SK-Mel-5 cells but not that of HTB-65 or CRL-11147 cells. PCNA mRNA, PCNA+ cells, PCNA staining intensity, and the OD value of HTB-72 melanoma cells were consistently decreased in the present of IL-9. IL-9 also increased TUNEL+ cells and the relative caspase-3 activity in HTB-72 melanoma cells. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The anti-proliferative effect of IL-9 on HTB-72 cells correlated with higher expression of anti-proliferative molecule p21. Its pro-apoptotic effect on HTB-72 cells correlated with higher expression of the pro-apoptotic molecule TRAIL. CONCLUSIONS: IL-9 inhibits melanoma HTB-72 cell growth by upregulation of p21 and TRAIL. Understanding the interactions between IL-9 and melanoma may help direct strategies for cytokine-based immunotherapy development.

Factors associated with radiosensitivity of cervical cancer.

Radiation therapy plays a critical role in women with advanced-stage cervical cancer worldwide, particularly in developing countries, and most of the time it may be the only available treatment. The efficacy of radiation largely depends on the radiosensitivity of the tumor. The high radiation dose associated with therapy for cervical cancer may have severe side-effects and low-dose radiation has little effect on cervical cancer. A safe and effective radiosensitizing agent is required to allow reduction of radiation doses used and of side-effects associated with radiation for cervical cancer. In recent years, great knowledge has been gained about the effects of apoptosis, cyclo-oxygenases, angiogenesis, hypoxia and temperature on radiation, making it possible to manipulate the radiation response of cervical cancer to achieve a better treatment outcome. In this mini review, some of these factors associated with the radiosensitivity of cervical cancer are discussed.

IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor.

Interleukin-35 (IL-35), an IL-12 cytokine family member, mediates the immune inhibitory function of regulatory T cells (Treg). We assayed the presence of IL-35 in paraffin-embedded human pancreas cancer (PCAN) and unexpectedly found IL-35 was expressed mainly by epithelial derived PCAN cells, but not by Treg. We further examined the expression and effect of exogenous IL-35 in human PCAN cell lines and found IL-35 promoted growth and inhibited apoptosis in PCAN cell lines. IL-35 induced proliferation correlated with an increase in cyclin B, cyclin D, cdk2, and cdk4 and a decrease in p27 expression, while inhibition of apoptosis was associated with an increase in Bcl-2 and a decrease in TRAILR1. We conclude IL-35 is produced by PCAN in vivo and promotes PCAN cell line growth in vitro. These results might indicate an important new role for IL-35 as an autocrine growth factor in PCAN growth.