CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10-/-CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133- population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133- metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133- cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24-), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133+ tumor cells might give rise to the more aggressive CD133(- )subset, which is also capable of tumor initiation in NOD/SCID mice.     

The role of F18-fluorocholine positron emission tomography/magnetic resonance imaging in localizing parathyroid adenomas

European Archives of Oto-Rhino-Laryngology - Preoperative localization of a parathyroid adenoma is usually obtained by the combination of ultrasound and scintigraphy with technetium-99m...     

Gynecological cancer incidence in a hospital population in Saudi Arabia: the effect of foreign immigration over two decades

Aim:  To determine if the incidence of female genital malignancies changed with foreign immigration.
Methods  Retrospective analysis of histopathology records of women with primary genital tract cancers attending a referral gynecological hospital over two decades from 1985 to 2004. Incidence rates for the combined population of foreign migrants and Saudi nationals were compared to rates among Saudi nationals alone. Outcome measures were incidence rates and incidence rate ratios.
Results:  The incidence of cervical cancer for the combined migrant and local Saudi population was 48.4%, while for Saudi nationals alone it was 33.5% (incident rate ratio [IRR]= 1.44, 95% CI 1.17–1.88, P  < 0.001). For vulvar cancer, the incidence was 1.2% versus 0.5% (IRR = 2.4, 95% CI 2.03–2.79, P  < 0.001). Endometrial cancer rate was lower in the combined population than in Saudi nationals alone (11.7% vs 18.0%, IRR = 0.65, 95% CI 0.27–1.02, P  < 0.04). There were no differences in incidence for gestational trophoblastic neoplasia, uterine corpus sarcoma, ovarian, and vaginal cancer. Incidence rate ratios differed between decades for cervical cancer (1.1/1.9, 0.58, 95% CI 0.21–0.89, P  < 0.001), vulvar cancer (4.2/1.8, 2.33, 95% CI 1.68–3.07, P  < 0.001), gestational trophoblastic neoplasia (1.4/1.0, 1.4, 95% CI 1.09–2.13, P  < 0.04), and uterine sarcoma (0.3/1.0, 0.03, 95% CI 0.012–0.041, P  < 0.02).
Conclusion:  The incidence of cervical and vulvar cancer increased among women presenting with gynecological malignancies. For cervical and vulvar cancer, uterine corpus sarcoma, and gestational trophoblastic neoplasia, incidence varied over time.     

Recommendations on prevention of infections during chimeric antigen receptor T-cell and bispecific antibody therapy in multiple myeloma

Chimeric antigen receptor T (CAR T) cell and bispecific antibody therapies have shown unprecedented efficacy in heavily pretreated patients with multiple myeloma (MM). However, their use is associated with a significant risk of severe infections, which can be attributed to various factors such as hypogammaglobulinemia, neutropenia, lymphopenia, T-cell exhaustion, cytokine-release syndrome and immune-effector cell-associated neurotoxicity syndrome. As these therapies have been recently approved by regulatory agencies, it is crucial to establish practical guidelines for infection monitoring and prevention until robust data from prospective clinical trials become available. To address this issue, a panel of experienced investigators from the Academic Consortium to Overcome Multiple Myeloma through Innovative Trials (COMMIT) developed consensus recommendations for mitigating infections associated with CAR T-cell and bispecific antibody therapies in MM patients.