We report a case of clear cell "sugar" tumour of the lung (CCTL) occurring in a 26-year-old lady. The patient was asymptomatic and the lesion was picked up in the course of a pre-employment medical examination. A well-defined 5 cm nodule in the right lower lobe was detected on routine chest X-Ray. Microscopical examination of the coin lesion showed clear cells containing abundant diastase-sensitive intracytoplasmic glycogen, as demohstrated with periodic acid-Schiff stains. Tumour immunoreactivity for HMB-45 and non-reactivity for cytokeratin support the histological diagnosis. To our knowledge, this is the first reported case of CCTL in Malaysia.
Malignant melanoma involving the gastrointestinal tract is diagnosed antemortem in only a small percentage of patients with the disease. Presenting symptoms are often non-specific, causing a diagnostic problem. The vast majority of such melanomas are metastatic from a cutaneous primary, however there is evidence that the tumour can arise de novo in the gastrointestinal system. We report a 74-year-old man with malignant melanoma with an unusual presentation simulating a symptomatic gastric ulcer. He presented with epigastric pain, haematemesis and melaena. Explorative laparotomy revealed a large ulcerated tumour with several pigmented satellite nodules in the proximal stomach, multiple ileal nodules and widespread nodal and liver metastases. Proximal gastrectomy and limited small bowel resection was performed. Histology revealed the tumour to be composed of nests of epithelioid cells with melanin pigment. The tumour cells showed immunohistochemical positivity for S100 protein and HMB45 antibodies. This report emphasizes that melanoma should be a diagnostic consideration in patients with gastric ulcer.
MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo, and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC.
A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.
The angiogenic potential of native skin (NS), keratinocytes single skin equivalent (SSE-K), fibroblasts single skin equivalent (SSE-F) and bilayered skin equivalent secreting angiogenic growth factors such as transforming growth factor beta1 (TGF-beta1), vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF) and basic fibroblast growth factor (bFGF) in the in vitro systems at 24, 48, 72 hours and 7 days was compared using Enzyme-Linked Immunosorbent Assay (ELISA). Bilayered skin equivalent exhibit highest release of growth factors within 24 hours to 7 days of culture compared to NS, SSE-K and SSE-F. This proved the potential of bilayered skin equivalent in producing and sustaining growth factors release to enhance angiogenesis, fibroblasts proliferation, matrix deposition, migration and growth of keratinocytes.
Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in several animal models, for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections. The administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA) also represents another potential application of the concept of the Id network. Limited experience in human trials using anti-Id to stimulate immunity against tumors has shown promising results. In this "counter-point" article, we discuss our own findings showing the potential of anti-Id antibody vaccines to be novel therapeutic approaches to various human cancers and also discuss where anti-Id vaccines may perform better than traditional multiple-epitope antigen vaccines.