Prognostic significance of osteosarcopenia in older adults with colorectal cancer.

Aim: Osteopenia and sarcopenia, features of the aging process, are recognized as major health problems in an aging society. This study investigated the prognostic impact of osteosarcopenia, the coexistence of osteopenia and sarcopenia, in older adults undergoing curative resection for colorectal cancer. Methods: We retrospectively reviewed data of older adults aged 65-98 y who had undergone curative resection for colorectal cancer. Osteopenia was evaluated by bone mineral density measurement in the midvertebral core of the 11th thoracic vertebra on preoperative computed tomography images. Sarcopenia was evaluated by measuring the skeletal muscle cross-sectional area at the third lumbar vertebra level. Osteosarcopenia was defined as the coexistence of osteopenia and sarcopenia. We explored the relationship of preoperative osteosarcopenia with the disease-free and overall survival after curative resection. Results: Among the 325 patients included, those with osteosarcopenia had significantly lower overall survival rates than those with osteopenia or sarcopenia alone (P < 0.01). In the multivariate analysis, male sex (P = 0.045), C-reactive protein-to-albumin ratio (P < 0.01), osteosarcopenia (P < 0.01), pathological T4 stage (P = 0.023), and pathological N1/N2 stage (P < 0.01) were independent predictors of disease-free survival, while age (P < 0.01), male sex (P = 0.049), C-reactive protein-to-albumin ratio (P < 0.01), osteosarcopenia (P < 0.01), pathological T4 stage (P = 0.036), pathological N1/N2 stage (P < 0.01), and carbohydrate antigen 19-9 (P = 0.041) were independent predictors of overall survival. Conclusion: Osteosarcopenia was a strong predictor of poor outcomes in older adults undergoing curative resection for colorectal cancer, suggesting an important role of osteosarcopenia in an aging society.

Association of a newly developed Cancer Cachexia Score with survival in Stage I-III colorectal cancer.

PURPOSE: Cancer cachexia, a complex multifactorial syndrome associated with sarcopenia, negatively affects the quality of life and survival in patients with several cancers. We aimed to develop a new score for cachexia assessment and evaluate its effectiveness in the classification of patients undergoing radical resection for colorectal cancer. METHODS: This study included 396 patients who underwent radical resection for Stage I-III colorectal cancer. To develop the Cancer Cachexia Score (CCS), we analyzed predictive factors of cachexia status related to the development of sarcopenia and incorporated significant factors into the score. We then evaluated the relationship between CCS and survival after radical resection for colorectal cancer. RESULTS: As body mass index (P < 0.001), prognostic nutritional index (P = 0.005), and tumor volume (P < 0.001) were significantly associated with the development of sarcopenia, these factors were included in CCS. Using CCS, 221 (56%), 98 (25%), and 77 (19%) patients were diagnosed with mild, moderate, and severe cancer cachexia, respectively. In multivariate analysis, severe CCS (P < 0.001), N stage 1-2 (P < 0.001), and occurrence of postoperative complications (P = 0.007) were independent predictors of disease-free survival. Age ≥ 65 years (P = 0.009), severe CCS (P < 0.001), and N stage 1-2 (P < 0.001) were independent predictors of overall survival. CONCLUSIONS: CCS may be a useful prognostic factor for predicting poor survival after radical resection in patients with Stage I-III colorectal cancer.

Light curves and colours of the ejecta from Dimorphos after the DART impact.

On 26 September 2022, the Double Asteroid Redirection Test (DART) spacecraft struck Dimorphos, a satellite of the asteroid 65803 Didymos1. Because it is a binary system, it is possible to determine how much the orbit of the satellite changed, as part of a test of what is necessary to deflect an asteroid that might threaten Earth with an impact. In nominal cases, pre-impact predictions of the orbital period reduction ranged from roughly 8.8 to 17 min (refs. 2,3). Here we report optical observations of Dimorphos before, during and after the impact, from a network of citizen scientists' telescopes across the world. We find a maximum brightening of 2.29 ± 0.14 mag on impact. Didymos fades back to its pre-impact brightness over the course of 23.7 ± 0.7 days. We estimate lower limits on the mass contained in the ejecta, which was 0.3-0.5% Dimorphos's mass depending on the dust size. We also observe a reddening of the ejecta on impact.

Feasibility of oral antibiotic prophylaxis in elective laparoscopic cholecystectomy during periods of limited cefazolin supply.

INTRODUCTION: In March 2019, the supply of cefazolin sodium (CEZ) became difficult owing to contamination of the drug substance. We investigated the efficacy and safety of the oral administration of cephalexin (CEX) in preventing infectious complications following elective laparoscopic cholecystectomy (LC). METHODS: From July 2018 to June 2019, 1 g of CEZ was administered intravenously within 30 min prior to LC (IV group). From July 2019 to June 2020, 0.5 g of CEX was administrated orally within 2 h prior to LC (oral group). We compared clinicopathologic variables and perioperative results between these two groups. RESULTS: During the period, 60 patients underwent elective LC; 35 from the oral group and 25 from the IV group. There was no significant difference in the surgical site infection (P = 0.37), distant infection (P = 0.23), and postoperative medical costs (P = 0.11) between both groups. Postoperative nausea and vomiting were significantly higher in the oral group (P = 0.04), whereas the C-reactive protein value on the first day after the operation was significantly lower in the oral group (P < 0.01). CONCLUSION: During the period of limited CEZ supply, oral administration of CEX may be an alternative antibiotic prophylaxis in LC.

[Pancreatobiliary Fistula with Jaundice-A Case Report].

An 80-year-old woman was admitted to our hospital due to jaundice. CT and MRCP revealed that the common bile duct and main pancreatic duct were dilatated due to a cystic lesion in the pancreatic head. Moreover, ERCP revealed the presence of a pancreatobiliary fistula and mucus discharge from the enlarged papilla. The patient underwent biliary and pancreatic drainage using plastic stents. However, the treatment was not effective because of the presence of the protein plug. The patient underwent EST because of her rejection to surgery. After the procedure, jaundice was resolved. We report this case with a review of the available literature.

Comparison of outcomes of single-incision and conventional laparoscopic cholecystectomy for cholecystitis requiring percutaneous transhepatic gallbladder drainage.

INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) has been accepted as a less invasive alternative to conventional laparoscopic cholecystectomy (CLC). However, the feasibility and safety of SILC for acute cholecystitis, especially in cases with percutaneous transhepatic gallbladder drainage (PTGBD), are still limited because of the technical difficulty of SILC. The aim of this study was to retrospectively evaluate the safety and feasibility of SILC compared to CLC for cholecystitis requiring PTGBD. METHODS: From 1 July 2017 to 8 June 2019, eight patients underwent SILC with PTGBD, and nine underwent CLC with PTGBD. The patients' data, including the operative time, total blood loss, conversion rate to laparotomy, and perioperative complications, were compared. RESULTS: In seven of eight patients, SILC was successfully performed. Only one patient required conversion to open surgery because necrosis prevented the cystic duct from being clipped. However, bile leakage occurred in this patient and was successfully treated with percutaneous drainage and antibiotics. In the CLC group, one patient required laparotomy but had no postoperative complications due to strong adhesion. One patient underwent reoperation for bile duct injury after the first operation. One other complication (ie, wound infection) was seen in the CLC group. There was no significant difference in the mean operative time and estimated blood loss between the SILC and CLC groups. CONCLUSION: With our gallbladder retraction method, SILC may be a relatively safe and feasible alternative to CLC for cholecystitis, even in cases requiring PTGBD.

Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.

The proper location and timing of Dnmt1 activation are essential for DNA methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono-ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and activation at DNA methylation sites. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the known ubiquitin-recognition structures. The two ubiquitins are simultaneously bound to the RFTS with a combination of canonical hydrophobic and atypical hydrophilic interactions. The C-lobe of RFTS, together with the K23Ub surface, also recognizes the N-terminal tail of H3. The binding of H3-K18Ub/23Ub results in spatial rearrangement of two lobes in the RFTS, suggesting the opening of its active site. Actually, incubation of Dnmt1 with H3-K18Ub/23Ub increases its catalytic activity in vitro. Our results therefore shed light on the essential role of a unique ubiquitin-binding module in DNA methylation maintenance.

A Case of Laparoscopic Resection for Carcinoma of the Gastric Remnant following Proximal Gastrectomy Reconstructed with Jejunal Interposition.

A 72-year-old Japanese man had a history of proximal gastrectomy for early gastric cancer located in the upper third of the stomach in 2007. Our usual treatment strategy for early gastric cancer in the upper third of the stomach in 2007 was open proximal gastrectomy reconstructing by jejunal interposition with a 10 cm single loop. Upper gastrointestinal fiberscopy for annual follow-up revealed a type 0-IIc-shaped tumor with ulcer scar, 4.0 cm in size, located in the gastric remnant near the jejunogastrostomy. A clinical diagnosis of cancer of the gastric remnant, clinical T1b(SM)N0M0, Stage IA, following the proximal gastrectomy was made and a laparoscopic approach was selected because of the cancer's early stage. Remnant total gastrectomy with D1 plus lymphadenectomy was carried out with five ports by a pneumoperitoneal method. Complete resection of the reconstructed jejunum was undergone along with the jejunal mesentery. Reconstruction by the Roux-en-Y method via the antecolic route was selected. Total operative time was 395 min and blood loss was 40 mL. Our patient was the first successful case of resection for carcinoma of the gastric remnant following proximal gastrectomy reconstructed with jejunal interposition in a laparoscopic approach.

Totally laparoscopic gastrectomy for early gastric cancer accompanied by huge hiatal hernia: A case report.

We herein present a case in which we used a totally laparoscopic approach for early gastric cancer accompanied by a huge hiatal hernia. An 80-year-old Japanese woman was referred with a chief complaint of dysphagia. A clinical diagnosis of early gastric cancer, T1b (SM) N0M0, stage IA, accompanied by hiatal hernia, was made. Distal gastrectomy with D1 plus lymphadenectomy was carried out. After the gastrectomy, the hernial sac was excised and the hernial orifice was closed. Reconstruction using the Roux-en-Y method was selected. The postoperative course was uneventful and she was discharged on postoperative day 10.

[Multidisciplinary Treatment for a Patient with Primary Malignant Melanoma Arising from the Stomach].

A 61-year-old woman was referred to our hospital with the complaint of severe dysphagia. Upper gastrointestinal endoscopy revealed an elevated tumor with an irregular surface located in the upper third of the stomach, and malignant melanoma was confirmed by biopsy specimens. Abdominal CT scan findings revealed that the tumor was invading the lateral segment of the liver and crus of the diaphragm. Total gastrectomy was combined with resection of the lateral segment of the liver and the crus of the diaphragm, and D2 lymphadenectomy and reconstruction by the Roux-en-Y method were carried out. Because of positive peritoneal washing cytology, monotherapy with dacarbazine, and combination therapy, including dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen citrate, were administered for treating the residual tumor. The patient died from peritoneal relapse 146 days after the initial surgery. Primary malignant melanoma arising from the stomach is reported as an extremely rare disease with a poor prognosis. In our case, multidisciplinary treatment including surgery and chemotherapy was insufficient to achieve long-term survival in a highly advanced malignant melanoma arising from the stomach.

[Effectiveness of chemoradiotherapy for a patient with local recurrence of advanced gastric cancer followed by curable gastrectomy].

We report here the effectiveness of chemoradiotherapy for a patient with local recurrence followed by curable gastrectomy. A 57-year-old man presented with a history of total gastrectomy with distal pancreatectomy and splenectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for advanced gastric cancer arising from the cardia. Esophageal intramural metastasis and lymph node metastasis around the right recurrent nerve were detected by chest-abdominal computed tomography and gastrointestinal endoscopy 27 months after the initial gastrectomy. Stable disease was achieved following 7 courses of chemotherapy using S-1 plus CDDP. Concurrent chemoradiotherapy including administration of S-1 and radiation of total 50 Gy (2 Gy/25 Fr) was selected for local tumor control. The patient was not able to eat solid food because of esophageal stenosis from regrowth of intramural metastasis of the esophagus 60 months after the chemotherapy. A WallFlex™ Duodenal Stent was placed to improve the dysphagia 67 months after chemotherapy. The patient died from recurrence of gastric cancer 69 months after completion of the initial chemotherapy and 2 months after the stent insertion.

N-terminally LRMK-linked HER-2 peptides, AE-37 [p776(774-788)] and AE-47 [Ava-F7(776-788)], aid differentiation of E75-TCR+CD8+ cells to perforin-positive cells.

The objective of this study was to discover whether the peptides LRMK and LRMK-Ava linked to the N-terminus of peptides HER-2 (774-788) and HER-2 (776-788), respectively, help differentiation of E75-TCR(+)CD8(+) cells. Activation was quantified in terms of proliferation of E75-TCR(+)CD8(+) cells expressing high, medium and low density amounts of the specific TCR. Differentiation to functional CD8(+) cells was quantified as induction of Perforin (Perf), the lytic-enzyme which mediates the effector function of CD8(+) cells, in E75-TCR(+)CD8(+) cells. Peripheral blood mononuclear cells (PBMCs) of 3 patients activated with E75(+)AE-37 and E75(+)AE-47 more greatly increased the number of E75-TCR(Hi) CD8(+)Perf(+) cells than PBMCs activated by AE-47 alone or AE-47(+) E75. E75 plus cytokines and cytokines alone activated more E75-TCR(Low) cells than did AE-37 and AE-47. E75(+) AE-37 and AE-37 also induced differentiation of small- and medium-size activated CD8(+) cells from BRC ascites, in allogeneic activation, to Perf(+) cells. Preferential differentiation of E75-TCR(+)CD8(+)Perf(+) cells in distinct patients by AE-37 and AE-47 indicates that cancer vaccines will benefit from such correct individual and disease-associated help. Additional studies using the natural peptides p776 and F7 are needed to understand whether the LRMK-(Ava) tetra-, or pentamer augments or inhibits differentiation of CD8(+) cells, compared with native, natural HER-2 peptides and/or protects CD8(+) cells activated by E75 and by other HLA-I bound peptides from death. Our findings also develop a model for uniform quantification of differentiated CD8(+) effectors.

Secreted interleukin-1alpha induces a metastatic phenotype in pancreatic cancer by sustaining a constitutive activation of nuclear factor-kappaB.

Transcription factor nuclear factor-kappaB (NF-kappaB) is constitutively activated in most pancreatic cancer tissues and cell lines but not in normal pancreas nor in immortalized/nontumorigenic human pancreatic ductal epithelial cells. Inhibition of constitutive NF-kappaB activation in pancreatic cancer cell lines suppresses tumorigenesis and tumor metastasis. Recently, we identified autocrine secretion of proinflammatory cytokine interleukin (IL)-1alpha as the mechanism of constitutive NF-kappaB activation in metastatic pancreatic cancer cell lines. However, the role of IL-1alpha in determining the metastatic potential of pancreatic tumor remains to be further investigated. In the current study, we stably expressed IL-1alpha in the nonmetastatic, IL-1alpha-negative MiaPaCa-2 cell lines. Our results showed that the secretion of IL-1alpha in MiaPaCa-2 cells constitutively activated NF-kappaB and increased the expression of NF-kappaB downstream genes involved in the different steps of the metastatic cascade, such as urokinase-type plasminogen activator, vascular endothelial growth factor, and IL-8. MiaPaCa-2/IL-1alpha cells showed an enhanced cell invasion in vitro compared with parental MiaPaCa-2 cells and induced liver metastasis in an orthotopic mouse model. The metastatic phenotype induced by IL-1alpha was inhibited by the expression of phosphorylation-defective IkappaB (IkappaB S32, 36A), which blocked NF-kappaB activation. Consistently, silencing the expression of IL-1alpha by short hairpin RNA in the highly metastatic L3.6pl pancreatic cancer cells completely suppressed their metastatic spread. In summary, these findings showed that IL-1alpha plays key roles in pancreatic cancer metastatic behavior through the constitutive activation of NF-kappaB. Our findings further support the possible link between inflammation and cancer and suggest that IL-1alpha may be a potential therapeutic target for treating pancreatic adenocarcinoma.

HER-2 peptides p776 and F7, N-terminal-linked with Ii-Key tetramer (LRMK) help the proliferation of E75-TCR+ cells: The dependency of help on the side chains of LRMK-extended peptide pointed towards the T cell receptor.

The objective of this study was to determine whether peptides consisting of the Ii-Key peptide LRMK linked to the N-terminal ends of HER-2 peptides would stimulate the expansion of antigen-specific E75-TCR+CD8+ cells. The peptides tested were N-acetylated and linked to an alpha-amide at the C-terminus; some of the peptides contained epsilon-aminovaleric acid (Ava) between the LRMK and the HER-2 peptide. Of the seven LRMK-HER-2 peptides tested to date, three effectively induced IFN-gamma production by peripheral blood mononuclear cells (PBMCs) from healthy donors and women with ductal carcinoma in situ. A fusion peptide, LRMK-Ava-HER-2(777-789), was more immunogenic than the natural HER-2(777-789) antigen, G89, with regard to IFN-gamma production. In combination with the CD8-activating peptide E75 [HER-2(369-377)] LRMK-p776 and LRMK-Ava-F7 induced the proliferation of E75-TCR(Med+Hi) CD8+ cells to a greater extent than did 1,000 or 5,000 nM of E75 alone, respectively. The induction effects were strongest at 600 nM for LRMK-p776 and 3,000 nM for LRMK-Ava-F7. At 3,000 nM, LRMK-p776 was cytotoxic to PBMCs. LRMK-p776 and F7 had a similar specificity and preferences for binding HLA-DR molecules. The molecular modeling of HLA-DR:LRMK-p776 and HLA-DR:LRMK-Ava-F7 complexes revealed the side chains of the peptides, which pointed towards the T-cell receptor. Differences in side chain orientation introduced by various N-terminal extensions of MHC class II-bound peptides should be important for directing CD4+ cells to stimulate CD8+ cells or for eliminating regulatory T cells in cancer immunotherapy.

LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis.

Most pancreatic cancer patients present with inoperable disease or develop metastases after surgery. Conventional therapies are usually ineffective in treating metastatic disease. It is evident that novel therapies remain to be developed. Transforming growth factor beta (TGF-beta) plays a key role in cancer metastasis, signaling through the TGF-beta type I/II receptors (TbetaRI/II). We hypothesized that targeting TbetaRI/II kinase activity with the novel inhibitor LY2109761 would suppress pancreatic cancer metastatic processes. The effect of LY2109761 has been evaluated on soft agar growth, migration, invasion using a fibroblast coculture model, and detachment-induced apoptosis (anoikis) by Annexin V flow cytometric analysis. The efficacy of LY2109761 on tumor growth, survival, and reduction of spontaneous metastasis have been evaluated in an orthotopic murine model of metastatic pancreatic cancer expressing both luciferase and green fluorescence proteins (L3.6pl/GLT). To determine whether pancreatic cancer cells or the cells in the liver microenvironment were involved in LY2109761-mediated reduction of liver metastasis, we used a model of experimental liver metastasis. LY2109761 significantly inhibited the L3.6pl/GLT soft agar growth, suppressed both basal and TGF-beta1-induced cell migration and invasion, and induced anoikis. In vivo, LY2109761, in combination with gemcitabine, significantly reduced the tumor burden, prolonged survival, and reduced spontaneous abdominal metastases. Results from the experimental liver metastasis models indicate an important role for targeting TbetaRI/II kinase activity on tumor and liver microenvironment cells in suppressing liver metastasis. Targeting TbetaRI/II kinase activity on pancreatic cancer cells or the cells of the liver microenvironment represents a novel therapeutic approach to prevent pancreatic cancer metastasis.

Mechanisms of synthetic serine protease inhibitor (FUT-175)-mediated cell death.

BACKGROUND: Constitutive activation of nuclear factor-kappaB (NF-kappaB) is a frequent molecular alteration in pancreatic cancer and a number of studies have suggested that constitutive NF-kappaB activity plays a key role in the aggressive behavior of this disease. In an attempt to identify an effective therapeutic agent for pancreatic cancer, the authors studied the role of FUT-175, a synthetic serine protease inhibitor, in the inhibition of NF-kappaB activation and the induction of apoptotic responses. METHODS: To examine the effect of FUT-175 on the inhibition of NF-kappaB and the induction of apoptosis in pancreatic cancer cell lines, Western and Northern blot analyses, electromobility shift (EMSA), luciferase reporter gene, DNA fragmentation, immunoprecipitation, in vitro kinase, small interfering RNA (siRNA), and chromatin immunoprecipitation (ChIP) assays were performed. RESULTS: In a time-dependent and dose-dependent manner, FUT-175 inhibited IkappaBalpha phosphorylation and NF-kappaB activation, thereby inhibiting the antiapoptotic activity of NF-kappaB. Simultaneously, FUT-175 up-regulated the expression of tumor necrosis factor receptor-1 (TNFR1), which in turn activated the proapoptotic caspase-8 and Bid pathways and induced apoptosis in pancreatic cancer cells. FUT-175-induced activation of Fas-associated death domain (FADD) and caspase-8 was suppressed by RNA interference-mediated inhibition of TNFR1 expression. Furthermore, expression of the transcription factor PEA3 was up-regulated by FUT-175 and was involved in FUT-175-mediated TNFR1 expression. CONCLUSIONS: These results suggested a possible mechanism by which FUT-175 may disrupt interconnected signaling pathways by both suppressing the NF-kappaB antiapoptotic activity and inducing TNFR-mediated apoptosis. Supported by this unique function as a NF-kappaB inhibitor and apoptosis inducer, this well-established synthetic serine protease inhibitor with as-of-yet poorly understood mechanisms of actions appears to be a potentially therapeutic agent for pancreatic cancer.

Novel natural immunogenic peptides from Numb1 and Notch1 proteins for CD8+ cells in ovarian ascites.

Notch is a plasma membrane receptor involved in the control of cell fate specification and in the maintenance of the balance between proliferation and differentiation in many cell lineages. Disruption of Notch has been implicated in a variety of hematological and solid cancers. Numb is also expressed in many adult mammalian cells. Adult cells divide symmetrically, and Numb is symmetrically partitioned at mitosis. The Numb-mediated regulation of Notch is believed to play a causative role in naturally occurring breast cancers. Reduction of Numb levels in breast tumors is regulated by proteasomal degradation. We reasoned that if the disregulated negative control of Notch by Numb protein is the consequence of Numb proteasomal degradation, then degradation of Numb can generate peptides which are transported, presented by MHC-I molecules. Surprisingly we found few candidate naturally processed peptides from Notch1, Notch2, and Numb1. CD8+ T cells expressing TCRs which specifically recognized peptides Notch1 (2112-2120) and Numb1 (87-95) were presented in the ascites of ovarian cancer patients. Many of these cells were differentiated and expressed high levels of Perforin. The natural immunogenicity of Notch1 and particularly of Numb1 suggests a mechanism of immunosurveillance which is overcome during tumor progression. Immunotherapy with tumor antigens from Notch and Numb should be important for treatment of cancer patients.

Synthetic microRNA designed to target glioma-associated antigen 1 transcription factor inhibits division and induces late apoptosis in pancreatic tumor cells.

PURPOSE: To determine whether the synthetic microRNAs (miRNA) could effectively target tumor cells we designed several miRNA complementary to glioma-associated antigen-1 (Gli-1) mRNA and investigated their ability to inhibit tumor cell proliferation. The sonic hedgehog pathway is an early and late mediator of tumorigenesis in epithelial cancers. Activation of sonic hedgehog signaling seems to precede transformation of tissue stem cells to cancerous stem cells, with the Gli-1 transcription factor functioning as a mediator of environmental signals. Inhibiting cancer cell proliferation by targeting the Gli-1 effector pathway is difficult to achieve by chemotherapeutic agents or short interfering RNA. EXPERIMENTAL DESIGN: We hypothesized that targeting the 3'-untranslated region of Gli-1 mRNA would effectively inhibit tumor cell proliferation. To test this hypothesis, we used synthetic miRNAs of our own design and corresponding duplex/small temporal RNAs by introducing three-nucleotide loops in the 3'-untranslated region Gli-1 sequence of high GU content. RESULTS: We found that miRNA (Gli-1-miRNA-3548) and its corresponding duplex (Duplex-3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells. The miRNAs mediated delayed cell division and activation of late apoptosis in MiaPaCa-2 cells. This is the first demonstration of inhibition of pancreatic tumor cell division by designed miRNA. CONCLUSIONS: Gli-1 miRNAs should significantly add to the general understanding of the mechanisms of metastasis and contribute toward the design of better treatments for epithelial cancers.

Implantation of rectal cancer in an anal fistula: report of a case.

A 53-year-old man who had had an anal fistula for 20 years was admitted to our hospital with a large intestinal obstruction. Barium enema and colonoscopy confirmed advanced rectal cancer and we palpated a soft tumor, 3 cm in diameter, with inflammatory induration on the right side of the rectum. After draining a perianal abscess caused by the anal fistula, we performed low anterior resection. Histological examination of the perianal necrotic tissue obtained during resection of the perianal tumor encompassing the anal fistula revealed adenocarcinoma. Since the histology of the perianal lesion was identical to that of the rectal cancer, a diagnosis of cancer implantation rather than carcinoma originating in the anal fistula was entertained. Although the recurrence of rectal cancer by mucosal implantation is not uncommon, the coincidental implantation of rectal cancer in an anal fistula is extremely rare.