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Mesothelioma, peritoneal [keywords]
- Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice. [Journal Article]
- PLoS One 2013; 8(11):e81919.
Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12) and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG). The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226) grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv) is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies.
- Surgical treatment of peritoneal carcinomatosis: current treatment modalities. [JOURNAL ARTICLE]
- Langenbecks Arch Surg 2013 Nov 19.
Selected patients with peritoneal surface malignancies (PSM) have been treated effectively by the combination of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).The purpose of this study is to summarize the treatment outcomes and general considerations regarding definitions and staging systems of current CRS and HIPEC modalities in malignant peritoneal mesothelioma and in secondary peritoneal malignancies such as peritoneal metastasis from appendiceal, colorectal, gastric, and epithelial ovarian cancers.Disease progression within the peritoneal cavity has in the past been regarded as a terminal event. Accumulating evidence underlines the therapeutic potential and the acceptable morbidity and mortality rates of CRS and HIPEC in selected patients.
- [Surgical Management of Peritoneal Surface Malignancy with Respect to Tumour Type, Tumour Stage and Individual Tumour Biology.] [JOURNAL ARTICLE]
- Zentralbl Chir 2013 Nov 15.
Peritoneal tumour dissemination is still considered as a terminal disease. For the last two decades, cytoreductive surgery (CRS) combined with intraoperative hyperthermic chemotherapy (HIPEC) has been popularised by Paul Sugarbaker almost doubling survival in selected patients compared with systemic chemotherapy alone. Nowadays, this particular treatment protocol is available in comprehensive cancer centres with reasonable mortality and morbidity. However, patient selection is still challenging. In general, CRS and HIPEC is indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei as well as in peritoneal metastases derived from gastrointestinal malignancies and ovarian cancers. Since systemic tumour spread is uncommon in patients with peritoneal metastases, peritoneal tumour dissemination was defined as localised disease within the "compartment abdomen". However, CRS and HIPEC are only beneficial as long as complete cytoreduction is achieved (CC-0 or CC-1). Histopathological parameters, the Sugarbaker peritoneal carcinomatosis index (PCI) and general condition of the patient have been established as patient selection criteria. In primary peritoneal cancers, individual tumour biology is the predominant criterium for patient selection as opposed to intraabdominal tumour load in peritoneal metastases derived from gastrointestinal cancers. In gastric cancer, CRS and HIPEC should be restricted to synchronous limited disease because of its biological aggressiveness. In patients with free floating cancer cells without macroscopic signs of peritoneal spread, however, CRS and HIPEC following preoperative "neoadjuvant" chemotherapy preserves chances for cure. So far, there is no general recommendation for CRS and HIPEC by clinical practice guidelines. In the recent S3 guideline for treatment of colorectal cancer, however, CRS and HIPEC have been included as possible treatment options.
- Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma. [JOURNAL ARTICLE]
- Oncogene 2013 Nov 18.
We identified a discrete number of microRNAs differentially expressed in benign or malignant mesothelial tissues. We focused on mir-145 whose levels were significantly downregulated in malignant mesothelial tissues and malignant pleural mesothelioma (MPM) cell lines as compared to benign tissues (pleura, peritoneum or cysts). We show that promoter hyper-methylation caused very low levels in MPM cell lines and specimens. Treatment of MPM cell lines with mir-145 agonists negatively modulated some protumorigenic properties of MPM cells, such as clonogenicity, cell migration and resistance to pemetrexed treatment. The main effector mechanism of the clonogenic death induced by mir-145 was that of accelerated senescence. We found that mir-145 targeted OCT4 via specific binding to its 3'-UTR. Increased intracellular levels of mir-145 decreased the levels of OCT4 and its target gene ZEB1, thereby counteracting the increase of OCT4 induced by pemetrexed treatment which is known to favor the development of chemoresistant cells. In line with this, reintroduction of OCT4 into mimic-145 treated cells counteracted the effects on clonogenicity and replicative senescence. This further supports the relevance of the mir-145-OCT4 interaction for the survival of MPM cells. The potential use of mir-145 expression levels to classify benign vs malignant mesothelial tissues and the differences between pemetrexed-induced senescence and that induced by the re-expression of mir-145 are discussed.Oncogene advance online publication, 18 November 2013; doi:10.1038/onc.2013.476.
- Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies. [JOURNAL ARTICLE]
- Eur J Surg Oncol 2013 Oct 16.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure.Between January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCI ± 11 and age ± 20 years) treated with CRS and HIPEC by laparotomy.Eight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210 min (150-300) vs 240 (210-360), with a median hospital stay of 12 days (9-18) vs 19 (13-33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group.Laparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay.
- Diffuse malignant peritoneal mesothelioma. [Journal Article]
- Kaohsiung J Med Sci 2013 Nov; 29(11):642-5.
Mesothelioma often originates in the pleura and less frequently in the peritoneum. This article describes a rare case of diffuse malignant peritoneal mesothelioma in a 54-year-old male construction worker who was admitted to our hospital with a 2-month history of progressive abdominal distention. Abdominal computed tomography revealed extensive peritoneal nodularity and omental cake along with massive ascites. Imaging findings initially suggested peritoneal carcinomatosis, primary peritoneal carcinoma, and tuberculous peritonitis. Laparoscopic biopsy of the omentum and peritoneum confirmed the diagnosis of malignant peritoneal mesothelioma of epitheloid type. Although systemic chemotherapy was administered, no tumor regression was found. The patient finally died of nosocomial infection.
- Synthesis and Antiproliferative Activity of Substituted 3[2-(1H-indol-3-yl)-1,3-Thiazol-4-yl]-1H-Pyrrolo[3,2-b]Pyridines, Marine Alkaloid Nortopsentin Analogues. [JOURNAL ARTICLE]
- Curr Med Chem 2013 Oct 31.
A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G2/M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr34 and to increase the cytotoxic activity of paclitaxel in STO cells.
- Intraperitoneal chemotherapy: Rationale, applications, and limitations. [JOURNAL ARTICLE]
- J Oncol Pharm Pract 2013 Oct 28.
Intraperitoneal chemotherapy, involving the administration of certain chemotherapeutic agents directly to the intraperitoneal cavity, was developed as a novel therapeutic strategy early in the 1950s. Intraperitoneal administration of chemotherapy results in higher intraperitoneal concentration of the cytotoxic medications and minimal systemic exposure than observed with intravenous administration, which in turn may increase the efficacy of these agents with substantial reduction in systemic toxicity. Intraperitoneal chemotherapy was used successfully in peritoneal surface malignancies, including malignant peritoneal mesothelioma, pseudomyxoma peritonei, malignant ascites, sarcomatosis, and peritoneal carcinomatosis from gastrointestinal and ovarian cancers. Pharmacists may play a major role in optimizing intraperitoneal chemotherapy through verification of chemotherapy order for proper doses, dilution, preparation, and administration. Moreover, pharmacists are medication experts who can provide other health care professionals with the necessary drug information.Despite the local application of chemotherapy, intraperitoneal chemotherapy is not free of systemic side effects and can be associated with serious complications. The benefits of intraperitoneal chemotherapy should be weighed against its potential harm to maximize efficacy and to minimize morbidity and mortality as much as possible. The aim of this article is to review the current available literature regarding the safety and efficacy of intraperitoneal chemotherapy in cancer treatment.
- A case of peritoneal mesothelioma masquerading as a urachal mass. [JOURNAL ARTICLE]
- ANZ J Surg 2013 Oct 28.
- Repeat Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy May Offer Survival Benefit for Intraperitoneal Mesothelioma: A Single Institution Experience. [JOURNAL ARTICLE]
- Ann Surg Oncol 2013 Oct 25.
Cytoreduction with heated intraperitoneal chemotherapy (HIPEC) has demonstrated improved overall survival (OS) in malignant peritoneal mesothelioma (MPM). The role of repeated HIPEC for MPM is less clear.An institutional review board-approved database of MPM patients was analyzed for clinical factors and outcomes.From June 2004 to March 2012, 29 patients underwent surgical treatment for mesothelioma. HIPEC was aborted in 3 and completed in 26; 8 underwent additional repeat HIPEC. The majority was male (62 %), median age 66 years. There was no significant difference in surgery duration, blood loss, or hospital-stay-duration between initial and repeat HIPEC. Cisplatin was the chemotherapy used. Complications occurred in 17 (65 %) initial and 6 (50 %) repeat HIPEC, with wound complications being most common. Reoperation was less common (4 % initial and 25 % repeat), and perioperative death was rare (4 % initial, 0 % repeat). Fourteen (54 %) initial and seven (58 %) repeat HIPEC patients received adjuvant chemotherapy. Median time from HIPEC to initiation of chemotherapy was not different between initial and repeat HIPEC (8.8 and 4.6 months, respectively, p = 0.68). Median treatment-free time (time from initial to repeat HIPEC or chemotherapy) also was not different between initial and repeat HIPEC (8.8 and 6.3 months, respectively, p = 0.92). Median OS for the cohort was 41.2 months. Patients who underwent repeat HIPEC had improved median OS (80 months) versus single HIPEC (27.2 months; p = 0.007). A lower peritoneal carcinoma index and complete cytoreduction were associated positively with OS.Cytoreduction and HIPEC for MPM are associated with longer OS. Patients who are candidates for repeat HIPEC may derive an even greater OS advantage.