Telomerase is a target for anticancer research because telomerase activity is closely correlated with malignancy. Inhibition of telomerase activity should increase telomere shortening, which destabilizes chromosomes, thus leading to cellular senescence and death. Extensive investigations have addressed the molecular mechanisms of telomerase activation in cancers. Based on results from these studies, various attempts have been made to inhibit telomerase activity using molecular techniques in cancer cells. Antisense oligonucleotides directed to human telomerase RNA, the dominant negative form of human telomerase reverse transcriptase (hTERT), hammerhead ribozymes that cut hTR and agents that interact with quadruplex DNA represent potential telomerase inhibitors. This review includes a summary of recent attempts to inhibit telomerase activity in cancer cells and a discussion of how these tools can be applied to cancer therapy, especially in combination with established anti-cancer agents.
Manuscript titleInfection with male and femaleTrichuris trichiuradiagnosed in a non-epidemic areaAuthors: Masaki Inoue1, Marin Ishikawa2, Sho Tanaka1, Xinhan Zhang1, Hiromi Okada3, Takuto Miyagishima11 Department of Gastroenterology, Kushiro Rosai Hospital, Kushiro, Japan.2 Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan.3 Department of Surgical Pathology, Kushiro Rosai Hospital, Kushiro, Japan.Corresponding author: Masaki Inoue, MD, PhD, Department of Gastroenterology, Kushiro Rosai Hospital, 13-23, Nakazonocho, Kushiro, Hokkaido 085-8533, Japan.Tel: +81-154-22-7191E-mail: mokomokomomon@gmail.comConsent statement: Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.Key words: endoscopy, Trichuris trichiura , parasite, whipwormConflict-of-interest statement: We have no financial relationships to disclose.Funding and Acknowledgement details: NoneExplanationA Burmese man in his 20s underwent colonoscopy at our hospital in Japan because of abdominal discomfort. He had come to Japan from Myanmar two years ago and had worked on a pig farm. He had had diarrhea for five months and was taking a drug for controlling intestinal function but had persistent abdominal discomfort. Blood samples showed elevated fractions of eosinophils (white blood cells 7900/μL, eosinophils 15.6%). Colonoscopy (PCF-H290ZI; Olympus, Tokyo, Japan) showed that there were four whipworms including one brown whipworm and three white whipworms in the cecum and ascending colon. The white whipworm was attached to the cecum mucosa ([Fig. 1], [Fig. 2]). The brown one was detected at the ascending colon. Magnified endoscopy and narrow band imaging showed that it had a stripe pattern and that its cranium was burrowing under the colonic mucosa ([Fig. 3]). The whipworms coiled themselves up and wound slowly in response to a stimulus. We removed all of them by using biopsy forceps. Histopathological examination revealed that the brown one was a female whipworm (Trichuris trichiura ) and the three white worms were male ([Fig. 4], [Fig. 5]). The female had a uterus with worm eggs. The egg inspection was negative. After oral administration of Mebendazole, his abdominal discomfort disappeared.T. trichiura infection is prevalent in tropical regions and non-epidemic in Japan. T. trichiura is thought to live for one to eight years as an adult [1]. Therefore, the worms that the patient was infected with in Myanmar could have lived for two years in Japan.T. trichiura parasitizes only humans through fecal-oral transmission. In non-epidemic areas, the frequency of endoscopic identification has been increasing due to the increasing number of immigrants from epidemic countries [2]. To prevent infection, it is important to pay attention to sanitary conditions such as soil and water sources [3].References[1] D.E. ElliotIntestinal wormsM. Feldman, L.S. Friedman, L.J. Brandt (Eds.), Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology/diagnosis/management (8th ed), Elsevier, Philadelphia (2006), pp. 2435-2457[2] Lorenzetti R, Campo SM, Stella F, Hassan C, Zullo A, Morini S. An unusual endoscopic finding: Trichuris trichiura . Case report and review of the literature. Dig Liver Dis. 2003 Nov;35(11):811-3. doi: 10.1016/s1590-8658(03)00455-9. PMID: 14674673.[3] Kattula D, Sarkar R, Rao Ajjampur SS, Minz S, Levecke B, Muliyil J, Kang G. Prevalence & risk factors for soil transmitted helminth infection among school children in south India. Indian J Med Res. 2014 Jan;139(1):76-82. PMID: 24604041; PMCID: PMC3994744.Figure 1A white whipworm in the cecum. Histopathological examination revealed that it was a male worm. The other two white whipworms were in the ascending colon.Figure 2A brown whipworm in the ascending colon. Histopathological examination revealed that it was a female worm.Figure 3A picture of the female worm obtained by using narrow band imaging showed that its cranium was burrowing under the colonic mucosa.Figure 4Histopathological image of a male whipworm.Figure 5Histopathological image of the female whipworm.
To estimate the risk of human papillomavirus (HPV) infection for cervical malignancies, we conducted a case-control study in Japan. Abnormal cervical cell (366) and normal cell samples (1562) were tested for the presence of HPV DNA using a new PCR-based test (LCR-E7 PCR). When single HPV infections were considered, 26 different HPV types were identified in normal cervices and in low-grade squamous intraepithelial lesions (LSIL); whereas HPV-16, -18, -31, -33, -35, -45, -51, -52, -56, -58 and -67 were detected in high-grade squamous intraepithelial lesions (HSIL) and in squamous cell carcinoma (SCC) of the cervix, and HPV-16 and -18 were detected in cervical adenocarcinoma. HPV-6 and -11 were detected in condyloma acuminatum tissue. In HSIL and SCC, HPV-16 was the most prevalent type and HPV-51, -52, and -58 were the next most prevalent; whereas HPV-39, -59, and -68 were not detected. Analysis by odds ratio (OR) revealed that HPV-11, -39, -42, -44, -53, -59, -62, and -66 (HPV-66: OR,139; 95% confidence interval (CI) = 6.7-168) were associated with LSIL; HPV-16, -18, -31, -51, -52 and -58 (HPV-16: OR, 69; 95%CI = 36-131) were associated with SCC; and HPV-16 and -18 (OR, 94; 95% CI = 28-317) were associated with adenocarcinoma. Multiple HPV infection was associated with LSIL (OR, 24; 95%CI = 13-44), HSIL (OR, 16; 95%CI = 8.4-32), and SCC (OR, 8.3; 95%CI = 3.2-22), although the prevalence decreased with the grade of the lesions. All results suggest that HPV-6 and -11 are condyloma types, HPV-16, -18, -31, -51, -52, -58, and perhaps -33, -35, -45, -56, and -67, are the high-risk HPV types, and many other types are LSIL-associated types in Japan. HPV typing and detection of multiple HPV infections in clinical samples may be useful as surrogate markers for cervical cell abnormalities.
Objectives/Hypothesis Transoral surgery (TOS) has become increasingly popular for patients with superficial hypopharyngeal squamous cell carcinoma (SCC). However, the number of patients in whom metachronous multiple SCC of the head and neck (HNSCC) occurs has also increased. In this study, we investigated whether multiple lugol‐voiding lesions (LVLs) in the pharyngeal background mucosa observed during TOS would be a biomarker of metachronous HNSCC. Study Design Retrospective study. Methods We examined 362 patients who underwent TOS for superficial hypopharyngeal carcinoma. Endoscopic images were reviewed in a blinded fashion by two endoscopists. LVLs in the pharyngeal mucosa were graded as follows: A, no lesions; B, 1 to 4 lesions; and C, ≥5 lesions per endoscopic view. Results Cumulative incidence curves of secondary HNSCC in the groups of grades A, B, and C revealed 3‐year incidence rates of 14.4%, 18.8%, and 29.3%, respectively ( P = .001 for A vs. C and P = .002 for B vs. C). Cumulative incidence curves of third HNSCC in the groups of grades A, B. and C revealed 5‐year incidence rates of 3.9%, 9.8%, and 19.6%, respectively ( P = .001 for A vs. C and P = .006 for B vs. C). Cumulative incidence curves of fourth HNSCC in the groups of grades A, B, and C revealed 7‐year incidence rates of 0%, 2.3%, and 13.2%, respectively ( P = .025 for A vs. C and P = .009 for B vs. C). Conclusions Multiple LVLs in the pharyngeal mucosa increase the risk of development of metachronous multiple HNSCC. Level of Evidence 3 (nonrandomized, controlled cohort/follow‐up study) Laryngoscope , 131:2036–2040, 2021
A man in his 50s presented with pitting edema of both lower legs and abdominal distension as his chief complaint. His personal medical history and family history were unremarkable, except that he was a heavy drinker consuming 66 g of alcohol per day and a heavy smoker. Blood tests upon admission showed slight hepatic dysfunction, thrombocytopenia, jaundice, hypoalbuminemia, and decreased coagulability. Tumor marker tests showed elevated levels of CA19-9 and PIVKA-II. Contrast-enhanced computed tomography revealed enhancement of multiple masses predominantly in the right lobe of the liver in the early phase, followed by diffuse enhancement of the entire liver in the delayed phase. Hepatic arteriography demonstrated large hemangioma-like lesions corresponding to the masses revealed by computed tomography. That findings seemed to be cotton wool appearance. On magnetic resonance images, there were multiple mass-like lesions that showed homogeneous or heterogeneous low signal intensity on T1-weighted images, and clearly high signal intensity on T2-weighted images. The findings were atypical and no definite diagnosis could be made. Hepatic failure then rapidly worsened, and the patient died on hospital day 20. Autopsy led to the diagnosis of hepatic angiosarcoma.
