Rab proteins are a group of ubiquitously expressed proteins that are responsible for intracellular transport of vesicles. Recent evidence has shown that certain Rab proteins are involved in the pathogenesis of cancer. We have recently shown that Rab25 is lost in a large fraction of breast cancer samples, particularly those derived from hormonally insensitive tumors. We have further investigated the role of Rab25 by re‐expressing Rab25 in tumorigenic cell lines and measuring the impact on tumor formation as well as on various molecular pathways through PCR array analysis. In vivo tumor growth of cell lines with re‐expressed Rab25 was markedly suppressed. Our data suggest that Rab25 acts through multiple pathways to enhance apoptosis and to suppress angiogenesis and invasion by modulating VEGF‐A and VEGFR‐1 expression. These findings suggest that Rab25 represents a novel class of cellular modulators that can influence both tumor initiation and the progression of the established tumors, thus ultimately affecting the biology of the malignant disease.
A novel breast cancer cell line (RAO‐3) was established by transduction of the Q61L mutant RAS into human mammary epithelial cells that were immortalized with catalytic subunit of telomerase (hTERT). The cells displayed anchorage‐independent growth and proliferation, and formed human mammary spindle cell carcinoma when injected into nude mice. Chromosome locus 1q22‐23 was partially duplicated and inverted on one of the 3 chromosomes present in the cell line. We report here that mutations of chromosome 1q22‐23 locus have resulted in the loss of RAB25 expression in the breast cancer cell line. Transduction of RAB25 into the breast cancer cell line arrests anchorage‐independent growth. We have also demonstrated loss of RAB25 in human breast tumor tissue. These data suggest that loss of RAB25 might contribute to tumorigenesis of breast cancer, and RAB25 is likely to be an important factor in the development of breast cancer. RAB25 could be used as biological marker of breast cancer and provides a target for gene replacement therapy.
Objectives: Non-melanoma skin cancer is the most common malignancy in US, with an annual incidence of in excess of 1.5 million cases. In the majority of cases, locoregional treatment is curative and systemic therapy is not indicated. Platinum-based chemotherapy regimens have been used most commonly in refractory cases. The use of cetuximab, a monoclonal antibody targeting epidermal growth factor receptor [EGFR], has been reported for skin cancer treatment. This current study evaluated eight cases of locally advanced and refractory basal cell or squamous cell cancers which were treated with cetuximab.
21 June 2010 in World Journal of Surgical Oncology
Background: To date, the clinical presentation and prognosis of mixed ductal/lobular mammary carcinomas has not been well studied, and little is known about the outcome of this entity. Thus, best management practices remain undetermined due to a dearth of knowledge on this topic. Methods: In this paper, we present a clinicopathologic analysis of patients at our institution with this entity and compare them to age-matched controls with purely invasive ductal carcinoma (IDC) and historical data from patients with purely lobular carcinoma and also stain-available tumor specimens for E-cadherin. We have obtained 100 cases of ductal and 50 cases of mixed ductal/lobular breast carcinoma. Results: Clinically, the behavior of mixed ductal/lobular tumors seemed to demonstrate some important differences from their ductal counterparts, particularly a lower rate of metastatic spread but with a much higher rate of second primary breast cancers. Conclusions: Our data suggests that mixed ductal/lobular carcinomas are a distinct clinicopathologic entity incorporating some features of both lobular and ductal carcinomas and representing a pleomorphic variant of IDC.
Platinum-based therapy is most often used to treat advanced cases of head and neck cancers, but only a small fraction of the patient population responds to cisplatin, with a median survival time of less than a year. Although gene signatures and molecular etiology of head and neck cancers have been previously described, none of them are predictive indicators of cisplatin treatment response in particular. Therefore, currently, there is a lack of clinically employable predictive indicators of the disease beyond HPV status to specifically predict patients' response to platinum-based therapy. It beckons a substantial effort to look for predictive indicators of cisplatin treatment response. In this regard, CD24 expression level appears to be a significant molecular phenotype of cisplatin-resistant residual cells in laryngeal carcinoma lines. CD24 expression level directly affects cisplatin sensitivity and affects the expression of critical apoptotic, stem and drug resistance genes. A relatively small retrospective patient tumor analysis suggests that CD24 high tumors go on to show an unfavorable response to cisplatin treatment. Overall, based on the strength of further analysis, CD24 presents a strong rationale to be utilized as a predictive indicator to stratify head and neck cancer patients for platinum-based therapy. It also provides a rationale for using CD24 as a therapeutic adjuvant target along with standard cisplatin therapy.
Pain is common among patients with head and neck cancer (HNC). However, there are very limited data on chronic pain among HNC patients treated with radiation therapy (XRT). In this retrospective study, we focused on the characteristics of chronic post-XRT pain in such patients. Post-XRT pain is common among HNC patients; however, we found discrepancy between frequency of treatment and frequency of chronic pain, suggesting poor documentation of pain in the medical records. Among patients who reported to have chronic post-XRT pain, most of them described having severe pain and used descriptors of neuropathic pain. Pharynx was the commonest site of cancer as well as the commonest site of cancer-related chronic pain; squamous cell carcinoma was the most frequent histological pattern, and opioids were used most often to treat such chronic pain. There was a significant association between chronic pain and number of sites of pain, and chronic pain was also associated with use of opioids.