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Salmonella have potential as anticancer therapeutic because of their innate tumor specificity. In clinical studies, this specificity has been hampered by heterogeneous responses. Understanding the mechanisms that control tumor col...
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Salmonella have potential as anticancer therapeutic because of their innate tumor specificity. In clinical studies, this specificity has been hampered by heterogeneous responses. Understanding the mechanisms that control tumor colonization would enable the design of more robust therapeutic strains. Two mechanisms that could affect tumor colonization are intracellular accumulation and intratumoral motility. Both of these mechanisms have elements that are controlled by the master motility regulator flhDC. We hypothesized that 1) overexpressing flhDC in Salmonella increases intracellular bacterial accumulation in tumor cell masses, and 2) intracellular accumulation of Salmonella drives tumor colonization in vitro. To test these hypotheses, we transformed Salmonella with genetic circuits that induce flhDC and express green fluorescent protein after intracellular invasion. The genetically modified Salmonella was perfused into an in vitro tumor-on-a-chip device. Time-lapse fluorescence microscopy was used to quantify intracellular and colonization dynamics within tumor masses. A mathematical model was used to determine how these mechanisms are related to each other. Overexpression of flhDC increased intracellular accumulation and tumor colonization 2.5 and 5 times more than control Salmonella, respectively (P < 0.05). Non-motile Salmonella accumulated in cancer cells 26 times less than controls (P < 0.001). Minimally invasive, ΔsipB, Salmonella colonized tumor masses 2.5 times less than controls (P < 0.05). When flhDC was selectively induced after penetration into tumor masses, Salmonella both accumulated intracellularly and colonized tumor masses 2 times more than controls (P < 0.05). Mathematical modeling of tumor colonization dynamics demonstrated that intracellular accumulation increased retention of Salmonella in tumors by effectively causing the bacteria to bind to cancer cells and preventing leakage out of the tumors. These results demonstrated that increasing intracellular bacterial density increased overall tumor colonization and that flhDC could be used to control both. This study demonstrates a mechanistic link between motility, intracellular accumulation and tumor colonization. Based on our results, we envision that therapeutic strains of Salmonella could use inducible flhDC to drive tumor colonization. More intratumoral bacteria would enable delivery of higher therapeutic payloads into tumors and would improve treatment efficacy.
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The U.S. Food and Drug Administration (FDA) announced on April 6 the approval of vandetanib to treat adult patients with late-stage (metastatic) medullary thyroid cancer (MTC) who are ineligible for surgery and who have disease th...
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The U.S. Food and Drug Administration (FDA) announced on April 6 the approval of vandetanib to treat adult patients with late-stage (metastatic) medullary thyroid cancer (MTC) who are ineligible for surgery and who have disease that is growing or causing symptoms. Show less
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Cervical cancer is the most common gynecologic malignancy and the fourth most common cancer in women worldwide. Over the last two decades, minimally invasive surgery (MIS) has emerged as the mainstay in the surgical management of ...
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Cervical cancer is the most common gynecologic malignancy and the fourth most common cancer in women worldwide. Over the last two decades, minimally invasive surgery (MIS) has emerged as the mainstay in the surgical management of early-stage cervical cancer, bringing advantages such as a lower operative morbidity and shorter hospital stay compared to open surgery, while maintaining comparable oncologic outcomes in numerous retrospective studies. Considering oncological patients, it is mandatory to assess the oncological outcomes and safety of this type of surgery. Moreover, there are different future outlooks on cervical cancer therapy, based on immunotherapy, target therapy, and poly-ADP-ribose polymerases (PARP) inhibitors in combination with each other, and in combination with standard chemotherapy and radiotherapy. The goal is to find an approach that is as personalized as possible.
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Melanoma is a malignant, the most aggressive and dreaded skin cancer. This form of cancer arises from melanocytes and may grow rapidly and metastasize. Melanoma predominantly occurs in skin, but could also be found in the mouth, i...
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Melanoma is a malignant, the most aggressive and dreaded skin cancer. This form of cancer arises from melanocytes and may grow rapidly and metastasize. Melanoma predominantly occurs in skin, but could also be found in the mouth, iris and retina of the eye. Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. It is highly resistant to traditional chemotherapy and radiotherapy, although modern biological therapies are showing some promise. Photodynamic therapy (PDT), as a novel effective modality of the treatment of skin cancers, opens up new possibilities in melanoma treatment also. Many experimental photodynamic therapy studies were performed. The results of many experiments indicate that that photodynamic therapy may be a promising tool for adjuvant treatment in advanced melanoma.
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In an article e-published on October 17 ahead of print in the International Journal of Radiation Oncology, Biology, Physics, Schwarz et al. from the Washington University School of Medicine (St. Louis, MO) reported on a study usin...
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In an article e-published on October 17 ahead of print in the International Journal of Radiation Oncology, Biology, Physics, Schwarz et al. from the Washington University School of Medicine (St. Louis, MO) reported on a study using 18F-FDG PET imaging to explore early metabolic response and patterns of failure in patients treated with definitive radiodierapy for cervical cancer. Show less
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Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prost...
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Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prostatic inhibin peptide (PIP). Findings of increased FSH concentrations and receptor expression in diseased prostate tissue suggest a role for FSH in prostate cancer growth. Not only does PIP suppress circulating levels of FSH, but it responds to and modulates prostatic FSH, suggesting a close interlinkage of these compounds in controlling both healthy and diseased prostate cells. Other focuses of endocrinologic research include androgen receptors, vitamin D, growth factors (including insulin-like growth factors I and II), and retinoids. Issues such as optimal therapy timing, intermittent administration, and the adoption of a multihormonal approach to the management of prostate cancer remain to be resolved.
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Abstract Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies have reported an increased risk of cancer in patients with diabetes. Furthermore, many patients with ...
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Abstract Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies have reported an increased risk of cancer in patients with diabetes. Furthermore, many patients with cancer already have diabetes, or develop hyperglycaemia as a consequence of the tumor or of cancer therapies, and coexisting diabetes confers a greater risk of mortality for many malignancies. Managing oncologic patients with diabetes is often complicated, since the co-existence of diabetes and cancer poses several complex clinical questions: what level of glycaemic control to achieve, which therapy to use, how to deal with glucocorticoid therapies and artificial nutrition, how diabetes complications can affect cancer management, which drug-drug interactions should be taken into account, or even how to manage diabetes at the end of life. In the clinical setting, both at hospital and at home, there are little agreed, evidence-based guidelines on the best management and criteria upon which clinical decisions should be based. A practical solution lies in the implementation of care networks based on communication and ongoing collaboration between Oncologists, Endocrinologists, and the nursing staff, with the patient at the centre of the care process. This manuscript aims to review the current evidence on the effect of cancer therapies on glucose metabolism and to address some of the more common challenges of diabetes treatment in patients with cancer.
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Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through th...
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Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondria] respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.
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The 45th annual meeting of the American Society of Clinical Oncology took place on May 29–June 2 in Orlando, Florida. Important clinical and research data in the field of breast cancer presented during this prestigious meeting ar...
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The 45th annual meeting of the American Society of Clinical Oncology took place on May 29–June 2 in Orlando, Florida. Important clinical and research data in the field of breast cancer presented during this prestigious meeting are reviewed in this material. The breast cancer sessions were marked by advances in prognostic and predictive markers, pharmacology, and, most notably, the treatment of metastatic breast cancer. A new class of drugs, the poly (ADP-ribose) polymerase (PARP) inhibitors, showed remarkable efficacy in the treatment of triple-negative breast tumors and BRCA1 and 2 associated tumours. New data confirmed that bevacizumab could be associated with different types of chemotherapy in the first-line treatment of metastatic breast cancer, with limited benefit in progression-free survival, but without improving overall survival. Long-term follow-up data confirmed the importance of urokinase tissue plasminogen activator/plasminogen activator inhibitor type I (uPA/PAI-1), as a prognostic factor for node-negative breast cancer patients. A large sentinel node study suggests that if a patient has a positive sentinel lymph node, axillary dissection remains the standard of care. Several studies investigated the influence of CYP2D6 inhibitors on the outcomes of patients with breast cancer receiving tamoxifen as adjuvant therapy.
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The 45th annual meeting of the American Society of Clinical Oncology took place on May 29-June 2 in Orlando, Florida. Important clinical and research data in the field of breast cancer presented during this prestigious meeting are...
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The 45th annual meeting of the American Society of Clinical Oncology took place on May 29-June 2 in Orlando, Florida. Important clinical and research data in the field of breast cancer presented during this prestigious meeting are reviewed in this material. The breast cancer sessions were marked by advances in prognostic and predictive markers, pharmacology, and, most notably, the treatment of metastatic breast cancer. A new class of drugs, the poly (ADP-ribose) polymerase (PARP) inhibitors, showed remarkable efficacy in the treatment of triple-negative breast tumors and BRCA1 and 2 associated tumours. New data confirmed that bevacizumab could be associated with different types of chemotherapy in the first-line treatment of metastatic breast cancer, with limited benefit in progression-free survival, but without improving overall survival. Long-term follow-up data confirmed the importance of urokinase tissue plasminogen activator/plasmi-nogen activator inhibitor type I (uPA/PAI-1), as a prognostic factor for node-negative breast cancer patients. A large sentinel node study suggests that if a patient has a positive sentinel lymph node, axillary dissection remains the standard of care. Several studies investigated the influence of CYP2D6 inhibitors on the outcomes of patients with breast cancer receiving tamoxifen as adjuvant therapy.
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