Non-small cell lung cancer has a devastating prognosis, and markers enabling a precise prediction of therapy response have long remained scarce. Better treatment monitoring would allow an individual's more effective patient adjusted therapy with lesser side effects and good clinical outcomes. In the present study, we monitored the serum cytochrome c levels pre- and post-chemotherapy of non-small cell lung cancer patients. Using highly sensitive enzyme-linked immunosorbent assay, we evaluated cytochrome c levels in serum of 100 non-small cell lung cancer and 100 healthy controls. We observed about threefold lower serum cytochrome c level in newly diagnosed non-small cell lung cancer patients than healthy individuals. Patients in advanced stages and grade 3 histological differentiation showed significantly low level of serum cytochrome c, and the lower levels were associated with worse survival outcome of non-small cell lung cancer patients. In addition, serum cytochrome c level was observed to be more than 13-fold higher after first cycle of conventional chemotherapy, wherein patients with higher level of serum cytochrome c before any therapy showed better response to chemotherapy in terms of significantly higher level of serum cytochrome c after first cycle of chemotherapy than patients with low level of serum cytochrome c at the time of diagnosis. Detection of serum cytochrome c levels at the time of diagnosis may be useful in suggesting disease severity and prognosis of the non-small cell lung cancer patients. Monitoring of serum cytochrome c might also serve as a sensitive apoptotic marker in vivo reflecting chemotherapy-induced cell death burden in patients with non-small cell lung cancer.
MDM2 protein is an important regulator of the p53 pathway and has a large effect on the anti-tumorigenic activity of the p53. Presently, we aimed to analyze the possible association of p53 and mdm2 in the development and progression of non-small cell lung cancer. In addition, impact of an important gene promoter polymorphism of MDM2 (T309G, rs 2279744) on its gene expression and ultimately of the TP53 was investigated in non-small cell lung cancer patients. A case-control study using peripheral blood samples of 100 non-small cell lung cancer patients and 100 cancer free healthy controls was conducted. Expression profile of MDM2 and TP53 gene were evaluated by using quantitative real time polymerase chain reaction assay, and MDM2 promoter polymorphism were analyzed by amplification refractory mutation system polymerase chain reaction. Non-small cell lung cancer patients expressed more than 6-fold increased mdm2 and about 7-folds decreased in p53 expression levels compared to healthy controls. Higher fold change increase of mdm2 and/or decrease of p53 were associated with advanced status and poor clinical outcome of the patients. A significant increase in mdm2 of about 14-folds and decrease in p53 of about 16.5-fold were observed among patients with MDM2 (309GG) genotype vs just 2.2-fold increase in mdm2 and 1.9-fold decrease in p53 among patients with MDM2 (309TT) genotype. In conclusion, present study demonstrated that MDM2 (309 T > G) polymorphism may be one of the important factors for the increased expression mdm2, which was associated with down-regulation of p53 at messenger RNA (mRNA) level and ultimately may contribute in the poor clinical outcome of the non-small cell lung cancer patients, thus may prove as a promising target for the treatment of non-small cell lung cancer at molecular level.
Despite advances in neurosurgery and radiotherapy, the prognosis of patients with glioblastoma multiforme remains poor. Reports in the literature about the radiosensitizing properties of paclitaxel stimulated the authors to conduct a study using paclitaxel concurrently with radiation in a group of 18 patients who had residual disease postoperatively. Paclitaxel was delivered weekly as an intravenous infusion in a dose of 60 mg/m2 along with radiation to the primary lesion. A total of 108 cycles of paclitaxel was given. All the patients tolerated the treatment well. The main side effects were haematological, and neuropathy which was self-limiting. The overall 1-year survival rate was 70%, with 12 patients alive at 13 months. The median survival has not yet been reached although it is more than 13 months. Thus, paclitaxel can be safely delivered concomitantly with radiation in patients with glioblastoma multiforme. Larger, randomized trials are required to establish the comparative efficacy of paclitaxel as a radiosensitizer in glioblastoma multiforme.
Breast cancer with multiple parenchymal brain metastases carries an extremely poor outcome. Cranial radiotherapy improves survival by only a few months and the role of systemic therapy is marginal and largely unexplored. We report a patient with recurrent carcinoma of breast presenting with multiple bilateral cervical nodes and brain metastases manifesting as a right hemiparesis and facial nerve palsy, who was treated with palliative whole brain irradiation and letrozole. At the follow up at 20 months, neurological function had fully recovered, and both cerebral and extracerebral lesions had completely resolved, with calcification of the cerebral lesions. This report suggests that letrozole has beneficial effects both in extracranial and intracranial disease in hormone responsive metastatic breast cancer.
Langerhans cell histiocytosis (LCH) is a disorder of clonal proliferation of dendritic cell mainly occurring in children. Spine involvement is rare. This usually presents with pain and torticollis when neck is involved. Histopathology with immunohistochemistry is confirmatory. Local curative therapy with excision or curettage is used for localized disease. Radiotherapy is usually reserved for selected cases. Systemic chemotherapy is the treatment of choice for widespread systemic disease. In this article, we present an unusual presentation of atlantoaxial LCH with mastoid involvement resulting in hearing loss as the first symptom and quadruparesis in a middle aged male patient, which was also associated with soft-tissue mass at the nape of the neck and deafness. The patient was treated with radical radiotherapy, which provided excellent response to the disease. Involvement of atlantoaxial joint and temporal bone associated with soft-tissue mass neck and deafness in a middle-aged man is an extremely rare clinical situation.
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