Studies on Ectopic ACTH-Producing Tumors: I. Measurement of ACTH in Tumor Tissue

A sensitive and relatively simple method for the extractionand measurement of ACTH by bioassay and radioimmunoassay fromtissues of nonendocrine tumors was established. ACTH in tumorswas extracted with acetic acid and partially purified by adsorptionon silicate. The minimum detectable value was 28 µU/gwet tissue by bioassay and 6 µU/g wet tissue by radioimmunoassay.ACTH in tumor tissue was measured by this method in 25 patientswith suspected ectopic ACTH producing tumor. ACTH was detectedboth by bioassay and radioimmunoassay in 13 patients but wasnot detected in the remaining 12 patients by neither method.This suggests that the method is reliable for the diagnosisof ectopic ACTH producing tumors.     

Management of Gastrointestinal Stromal Tumors: Looking Beyond the Knife. An Update on the Role of Adjuvant and Neoadjuvant Imatinib Therapy

Background

Gastrointestinal stromal tumors (GISTs) have traditionally been treated with surgical resection alone resulting in high rates of recurrence. However, the discovery of imatinib efficacy in GIST has revolutionized its management.

Discussion

Imatinib may be used as neoadjuvant therapy with the goal of reducing tumor size, minimizing surgical morbidity and, in some cases, rendering inoperable cases operable. In addition, imatinib use in the adjuvant setting to eradicate micrometastases and prevent recurrence has shown promising results in reducing relapse rates. Appropriate patient selection and optimal dose and duration of imatinib therapy remain undecided and require further investigation. We present a literature review and a case report of our patient with a symptomatic gastric GIST managed successfully utilizing neoadjuvant imatinib therapy, laparoscopic limited resection, and adjuvant imatinib therapy.     

Studies on carcinogenesis of human prostate. III. Long-term explant culture of normal prostate and benign prostatic hyperplasia: transmission and scanning electron microscopy

Ultrastructural changes in normal human prostate and benign prostatic hyperplasia (BPH) during long-term explant culture were compared. Explants of normal prostate obtained at immediate autopsy of young adults of BPH obtained at the time of surgery were maintained as long as 24 weeks in vitro. Ultrastructural changes occurring in epithelial cells during culture were monitored by transmission and scanning electron microscopy. Essentially identical results were found for normal prostate and BPH. During the first week of culture, secretory epithelial cells degenerated and sloughed into the acinar lumen, resulting in an accumulation of necrotic debris. During this period, however, epithelial cells with ultrastructural characteristics of basal cells remained viable, repopulated glandular structures, migrated from glands and ducts, and epithelialized adjacent cut surfaces, eventually covering the explant. On explant surfaces, these basal cells initially were squamous-like, but they later became typically cuboidal, polygonal, or sometimes columnar and formed an epithelium, two cells or more thick. Epithelium with similar features lined acini within explants. Epithelial cells at the surface or within explants were distinguished by the presence of microvilli, junctional complexes, multiple Golgi complexes, well-developed rough endoplasmic reticulum, polyribosomes, nuclei with prominent nucleoli, orthodox mitochondria, scattered tonofilaments, and a basal lamina. Some epithelial cells extended from the lumen to the basal lamina; others were oriented along the basal lamina and did not extend to the lumen. By 1--2 weeks in vitro, these epithelial cells began synthesis of mucus-like material. At later intervals of culture, microvilli were shortened and mucosubstances were reduced. During culture, the stroma became progressively hypocellular and necrotic. In summary, explant-cultured epithelial cells of normal human prostate or BPH were similar ultrastructurally and were found to originate from basal cells, which alone survive culture conditions.     

Studies on a gross-virus-induced lymphoma in the rat. III. Optimisation, specificity and applications of the in vitro immune response.

Conditions are described for optimal stimulation in vitro of lymphocytes from rats primed in vivo with syngeneic MuLV-G leukaemia cells. Cultures generate effector cells which show high cytotoxic activity against leukaemic cells. Specific stimulation can be obtained with leukaemic cells and with disrupted MuLV. Leukaemic cells, normal spleen cells and the viron internal protein p30 competitively inhibit effector cells, but purified virus exerts non-specific inhibition. These findings are interpreted as supporting the hypothesis that virion antigens constitute a major target of anti-tumour cytotoxic immunity.     

Rationale and Approaches to the Prevention of Smoking-Related Diseases: Overview of Recent Studies on Chemoprevention of Smoking-Induced Tumors in Rodent Models

Tobacco smoke plays a dominant role in the epidemiology of lung cancer, cancer at other sites, and a variety of other chronic diseases. It is the leading cause of death in developed countries, and the global burden of cancer is escalating in less developed regions. For a rational implementation of strategies exploitable for the prevention smoking-related diseases, it is crucial to elucidate both the mechanisms of action of cigarette smoke and the protective mechanisms of the host organism. The imperative primary prevention goal is to avoid any type of exposure to smoke. Epidemiological studies have shown that a decrease in the consumption of cigarettes can be successful in attenuating the epidemic of lung cancer in several countries. Chemoprevention by means of dietary and/or pharmacological agents provides a complementary strategy aimed at decreasing the risk of developing smoking-associated diseases in addicted current smokers, who are unable to quit smoking, and especially in involuntary smokers and ex-smokers. The availability of new animal models that are suitable to detect the carcinogenicity of cigarette smoke and to assess the underlying molecular mechanisms provides new tools for evaluating both safety and efficacy of putative chemopreventive agents.     

Sarcoma classification: An update based on the 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone

The 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone incorporates changes in tumor classification, as well as new genetic insights into the pathogenesis of many different tumor types that have emerged over the 11 years since the publication of the prior volume. This article reviews changes in the classification of soft tissue and bone sarcomas as well as tumors of intermediate biologic potential in the 2013 World Health Organization volume, new molecular insights into these tumors, and associated surgical and clinical implications. Cancer 2014;120:1763–1774 . © 2014 American Cancer Society.     

Genotoxicity Testing and Biomarker Studies on Surface Waters: An Overview of the Techniques and Their Efficacies

Rapid industrialization, use of modern agriculture practices, and fast urbanization vis-a-vis indiscriminate use of xenobiotics have led to the serious problems of water pollution in India and abroad. The complexicity of the pollutants in environmental samples demands a multitude of genotoxicity testing with increasing simplicity, sensitivity, and affordability. Moreover, various pollutants mutually affect their own toxic behavior, which complicates the problem of risk assessment. An overview, highlighting the genotoxicity testing system, such as Ames plate incorporation test, Ames fluctuation test, E. coli survival assay, Allium cepa toxicity/genotoxicity test, comet assay, and plasmid nicking assay, is presented in this article, and a comparison has been made to estimate the efficacy of these genotoxicity bioassays performed on some surface waters. Some work on toxicity biomarkers vis-a-vis studies on surface waters has also been included in the present review.     

Wirkungen von Ketoconazol auf das Immunsystem III. In vitro-Testungen von Ketoconazol und Therapie-Verlaufskontrollen bei chronischen Dermatophytosen/Effects of Ketoconazole on the Immune System III. In Vitro Drug Testing and Follow-up Studies in Chronic Dermatophytoses

Zusammenfassung: Die Resultate der In-vitro Testung von Ketoconazol sowie Therapiever-laufskontrollen unter Ketoconazol von 7 Patienten mit Dermatophytosen werden vorgestellt Es gelang, eine "krankheitstypische" Immunreaktion herauszufinden, die sich im Falle des Ansprechens auf die Therapie Normwerten angleicht Wir konnten beobachten, daß eine Normalisierung der Befunde unter Therapie mit einem gleichartigen In-vitro-Effekt von Ketoconazol vor Therapiebeginn korrelierbar war. Kulturen mononukleärer Zellen der Patienten fielen durch erhöhte spontane Proliferationen, durch spontane IFNγ-Synthese sowie spontane Interleukinsynthese auf.
Die Hemmung der Spontanproliferation durch Ketoconazol in vitro korrelierte mit der späteren Ansprechbarkeit der Patienten auf die Therapie.
Summary: We present the results of in vitro testing of ketoconazole sensitivity in comparison to follow-up studies under ketoconazole therapy of 7 patients suffering from chronic dermatophytosis. We are able to demonstrate an "illness-related" immuno-reactivity of patients' mononuclear cells which come back to normal levels in the case of successful therapy with ketoconazole. The normalisation of immune parameters under therapy was correlated to analogous in vitro effects of ketoconazole prior to therapy. Patients' lymphocytes proliferate spontaneously, secrete IFNγ and interleukins, also spontaneously. The reduction of spontaneous proliferation by ketoconazole in vitro was correlated to successful ketoconazole therapy.     

Ovarian Sertoli Leydig cell tumours in children and adolescents: An analysis of the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT)

ObjectiveTo analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification.PatientsForty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n = 23), French TGM protocols (n = 10), Italian Rare Tumour Project (TREP) registry (n = 6), and the Polish Pediatric Rare Tumour Study group (n = 5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO).ResultsMedian age was 13.9 (0.5–17.4) years. All patients underwent resection by tumour enucleation (n = 8), ovariectomy (n = 17), adenectomy isolated (n = 18) or with hysterectomy (n = 1). FIGO-stage: Ia 24 pts., Ic 17 pts., II/III 3 pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic–III), eight relapsed, and five patients died. Eleven patients were initially treated with two to six cycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62 months, event-free survival is 0.70 ± 0.07, relapse-free survival 0.81 ± 0.06 and overall survival 0.87 ± 0.05.ConclusionsPrognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated.     

Update on the Colon Health and Life-Long Exercise Change Trial: A Phase III Study of the Impact of an Exercise Program on Disease-Free Survival in Colon Cancer Survivors

The Colon Health and Life-Long Exercise Change (CHALLENGE) trial is evaluating the effects of a 3-year exercise program on disease-free survival in 962 patients with resected high-risk stage II or stage III colon cancer. The purpose of this commentary is to provide an update on the CHALLENGE trial. As of December 31, 2013, the trial had randomized 250 patients in 20 Canadian centers and 26 Australian centers, with further expansion planned. Early barriers to accrual are reported and strategies to improve accrual are discussed. Of the 250 patients randomized to date, 89 % have stage III colon cancer, 56 % were treated with leucovorin/5-fluorouracil/oxaliplatin-based chemotherapy, 58 % have a body mass index of at least 27.5 kg/m², 53 % are women, and the median age is 60 years. The CHALLENGE trial remains the only randomized controlled trial in colon cancer survivors that is examining the effects of an exercise program on disease-free survival.     

Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial--the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group.

PURPOSE: To assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to solid tumors other than breast or prostate cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive zoledronic acid (4 or 8 mg) or placebo every 3 weeks for 9 months, with concomitant antineoplastic therapy. The 8-mg dose was reduced to 4 mg (8/4-mg group). The primary efficacy analysis was proportion of patients with at least one skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. Secondary analyses (time to first SRE, skeletal morbidity rate, and multiple event analysis) counted hypercalcemia as an SRE. RESULTS: Among 773 patients with bone metastases from lung cancer or other solid tumors, the proportion with an SRE was reduced in both zoledronic acid groups compared with the placebo group (38% for 4 mg and 35% for 8/4 mg zoledronic acid v 44% for the placebo group; P =.127 and P =.023 for 4-mg and 8/4-mg groups, respectively). Additionally, 4 mg zoledronic acid significantly increased time to first event (median, 230 v 163 days for placebo; P =.023), an important end point in this poor-prognosis population, and significantly reduced the risk of developing skeletal events by multiple event analysis (hazard ratio = 0.732; P =.017). Zoledronic acid was well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and vomiting. CONCLUSION: Zoledronic acid (4 mg infused over 15 minutes) is the first bisphosphonate to reduce skeletal complications in patients with bone metastases from solid tumors other than breast and prostate cancer.