Journal Issue: Vol. 12, No. 1 - January 2013
Editorial
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Manuscript
Loss of MKK4 Expression in Ovarian Cancer: A Potential Role for the Epithelial to Mesenchymal Transition
In the current study, we investigated the mechanism relating down-regulation of MKK4 expression to development of ovarian cancer. Over-expression of the MKK4 gene in TOV-21 G cells, a line with homozygous deletion of MKK4, resulted in morphologic changes in which cells growing in a scattered, fibroblast-like pattern formed tightly packed colonies. Based on a wound healing assay and a Matrigel invasion assay, we determined that both motility and invasiveness of MKK4-transfected TOV-21G cells were significantly reduced compared to control vector-transfected cells. To confirm that MKK4 expression related to tumor invasion resulted from an epithelial to mesenchymal transition (EMT)-like morphological change, we used two independent but complementary approaches. MKK4 gene knockdown in MDAH 2774 cells over-expressing MKK4 increased invasion activity. Additionally, engineered expression of MKK4 in SKOV3 cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of TOVG-21G. Interestingly, we found that MKK4 up-regulation caused down-regulation of phosphorylated NF-kB and Twist, as well as up-regulation of E-cadherin, in TOVG-21G and SKOV3 cells. Reciprocal results were obtained in MDAH 2774 cells with MKK4 knockdown. Our results suggest that MKK4 down-regulation causes increased phosphorylation NF-kB. This promotes Twist over-expression, resulting in E-cadherin down-regulation that induces EMT in ovarian cancer.
The Obesity Epidemic and the Oncological Burden: an Australian Perspective.
The prevalence of obesity is rising in Australia and abroad. Evidence shows that there are clear links between obesity and cancer. Obesity is thought to directly and indirectly play a role in carcinogenesis. Furthermore it complicates the diagnosis and treatment of cancer, and lowers the prognosis of those with cancer. With the provision of cancer services in Australia already struggling to meet the demands of a widespread population, this obesity epidemic is likely to further exacerbate resources. Prompt action is needed to target obesity prevention and management.
The Administration of the Irinotecan with Oxaliplatin, Actinomycin and Methotrexate may not be Feasible for Relapsed Germ Cell Tumours with Poor Prognosis.
A phase II single arm clinical trial was conducted in patients with relapsed germ cell tumours (GCT) using a combination of pegfilgrastim, actinomycin D, high dose methotrexate, irinotecan ,oxaliplatin [GAMIO]. The aims of this study were to establish response rates to GAMIO by investigating the safety and efficacy of combination of drugs. The planned sample size was 47. However, only five patients were recruited into the trial before recruitment was closed prematurely. There was a major drug interaction which caused severe diarrhoea and significant neutropenia and thrombocytopenia. Three patients out of the five died from serious adverse reactions (SAR) of the study treatment. One patient had a negative tumour marker response. Both the median overall survival and progression-free survival for this group of patients were 1.94 months. We concluded that the administration of the irinotecan with oxaliplatin, actinomycin and methotrexate may not be feasible.
Dawn for Personalized Therapy in Non-small Cell Lung Cancer
Before 2009, advanced non-small-cell lung cancer (NSCLC) was one disease entity that was treated by cytotoxic chemotherapy, which provided a response rate of 20-35% and a median survival time (MST) of 10-12 months. In 2004, it was found that activating mutations of the epidermal growth factor receptor gene (EGFR) were present in a subset of NSCLC, and that tumors with EGFR mutations were highly sensitive to EGFR tyrosine kinase inhibitors (TKI). In 2009, the phase III study NEJ 002 compared gefitinib with chemotherapy as first-line therapy in EGFR mutated NSCLC, and confirmed as the primary end point that progression-free survival (PFS) in the gefitinib group was significantly longer than that in the carboplatin plus paclitaxel group (10.8 versus 5.4 months, hazard ratio [HR] = 0.30, P < 0.001). Although the NEJ 002 showed identical MST between the arms (27.7 months versus 26.6 months, HR = 0.89), quality of life was maintained much longer in patients treated with gefitinib, indicating that gefitinib should be considered as the standard first-line therapy in advanced EGFR-mutated NSCLC. Since 2009, a new step has been introduced in the treatment algorithm for advanced NSCLC, in which three factors of driver gene mutations, histology, and performance status (PS) plus age must be considered: Driver genes of EGFR mutations and EML4-ALK will be screened in the recent future, Squamous versus non-squamous histology is now divided in order to judge indications for pemetrexed and bevacizumab, and PS plus age are still important clinical indicators.
Primary Hodgkin Lymphoma of Cecum in a Patient with Crohn’s Disease: Case Report and Review of the Literature
Crohn’s disease is an idiopathic, chronic inflammatory disease of the gastro-intestinal tract (GIT) primarily affecting the small intestine and colon. Hodgkin lymphoma is an extremely uncommon complication of Crohn’s disease, with only 12 cases being reported till date. The pathogenesis of lymphoma in Crohn’s disease is unexplained, with factors like chronic inflammation, immune dysregulation, presence of Ebstein-Barr virus or immune suppressive therapy being postulated as mechanistic factors by different authors. We describe here an unusual case of primary gastrointestinal Hodgkin lymphoma in cecum, diagnosed in a 69 years old female patient with Crohn’s ileocolitis. A histological diagnosis of classical Hodgkin lymphoma, mixed cellularity subtype was given; and confirmed by the presence of typical CD30 positive Reed-Sternberg cells on immunohistochemical staining.
Myoepithelioma (Myoepithelial Carcinoma) of the Breast: Case Reports
Myoepithelial carcinoma of the breast is a rare condition. Here, are 2 cases of malignant myoepithelial documented. Both were 51 year-old Kuwaiti women, presenting with abnormal breast masses. The first patient underwent mastectomy while the second patient underwent lumpectomy followed by mastectomy for narrow margins. The tumours were clinically, radiologically and macroscopically demarcated. Diagnosis was made based on histological and immunohistochemical studies. Both cases were positive for α-smooth muscle actin, S-100ptn and one case was positive for Vimentin and the other case was positive for Epithelial Membranous Antigen (EMA). From these findings the cases were diagnosed with malignant Myoepithelioma. One case consisted microscopically of tumour cells with clear cytoplasm, possibly making it one of 3 reported cases of clear cell myoepithelial carcinoma. One case locally recurred and metastasized, while the other is still newly diagnosed and under follow-up. Myoepithelial tumours are generally considered benign but do have a spectrum of behaviour with a potential for local recurrence and rarely distant metastses.
Case Report of Largest Primary Intrathoracic Desmoid Tumour with Review of Literature
Case of dumbbell shaped desmoid tumour of intrathoracic location, size 28x25x15 cm. operated with removal of 3rd 4th & 5th ribs. Review of literature done shows 24 reported cases, ours is largest one. Literature supported surgical excision as primary treatment but radiation, chemotherapy and hormonal therapy were also reported in some studies with varying success. Desmoid tumours are soft tissue neoplasms arising from fascial or musculo-aponeurotic structure. Most reported thoracic desmoids tumours originate from the chest wall. However, intrathoracic desmoids tumours are rare3 they are classified as benign as they do not metastasize. Desmoid Tumour account for approximately 3.5% of fibrous tumours, 0.3% of all solid tumours6 and only 0.03% of all the neoplasms.7 Chest wall desmoids account for approximately 20% of all desmoid Tumour. Surgical resection remains the mainstay of treatment with chest wall reconstruction when required, with recurrence rate of 25 - 40%. Reconstruction can be done by prolene mesh but use of titanium ribs is also documented. Some studies also reveal occasional spontaneous regression. In recurrent cases or cases with incomplete resection repeat resection or radiation after surgery approaches control rate of 75 - 80%. Some also document role of chemotherapy and hormonal therapy like anti-estrogens.
