Abnormal expression of MHC class I molecules in malignant cells is a frequent occurrence that ranges from total loss of all class I antigens to partial loss of MHC specific haplotypes or alleles. Different mechanisms are described to be responsible for these alterations, requiring different therapeutic approaches. A complete characterization of these molecular defects is important for improvement of the strategies for the selection and follow-up of patients undergoing T-cell based cancer immunotherapy.  Precise identification of the mechanism leading to MHC class I defects  will help to develop new personalized patient-tailored treatment protocols. There is significant new research on the prevalence of various patterns of MHC class I defects and the underlying molecular mechanisms in different types of cancer. In contrast, few data is available on the changes in MHC class I expression during the course of cancer immunotherapy, but the authors have recently made discoveries that show the progression or regression of a tumor lesion in cancer patients undergoing immunotherapy depends on the molecular mechanism responsible for the MHC class I alteration and not on the type of immunotherapy used. According to this notion, the nature of the preexisting MHC class I lesion in the cancer cell has a crucial impact on determining the final outcome of cancer immunotherapy. This SpringerBrief will present how MHC class 1 is expressed, explain its role in tumor progression, and its role in resistance to immunotherapy. ​

This SpringerBrief is comprehensive account of the functions and effects of the Epstein-Barr virus (EBV) EBNA1 protein that relate to EBV-associated cancers and evidence for EBNA1 contributions to these cancers.   EBNA1 was the first EBV protein detected and the most critical for EBV latent infection. EBNA1 fulfills multiple functions at EBV genomes which have been described in many (sometimes confusing) reports over the last 28 years. While these were initially thought to be the only roles of EBNA1, many reports in recent years have shown that EBNA1 also directly affects cellular processes in ways that would be expected to contribute to oncogenesis. However, the degree to which EBNA1 promotes cell survival and oncogenesis in various types of human tumours is not entirely clear and a matter of debate. This book offers a current synopsis of EBNA1 functions in EBV latency, including functions in DNA replication, mitotic segregation and transcription. Mechanisms of these EBNA1 functions is also discussed as well as implications for tumourigenesis. In addition, the cellular effects of EBNA1 will be reviewed, including how EBNA1 manipulates specific cellular proteins and relationships to EBV-associated lymphomas and carcinomas.

Obesity is a risk factor for breast cancer in older women. A number of adipose-derived and obesity-related factors have been shown to affect tumour cell growth. These include adipokines, insulin, IGF-1 and oestrogens. The majority of obesity-related postmenopausal breast cancers are oestrogen-dependent. Since the ovaries no longer produce oestrogens after menopause, and that circulating levels are negligible, it is evident that it is the oestrogens produced locally within the breast adipose that are responsible for the increased growth of breast cancer cells. Aromatase is the enzyme that converts androgens into oestrogens and its regulation is dependent on the activity of a number of tissue-specific promoters. Targeting oestrogen biosynthesis in obesity may be useful for the prevention of breast cancer. Aromatase inhibitors are efficacious at treating postmenopausal breast cancer and recent studies suggest that they may also be useful in the prevention setting. However, these compounds inhibit the catalytic activity of aromatase and as a consequence lead to a number of undesirable side-effects, including arthralgia and possible cognitive defects due to inhibition of aromatase in the bone and brain, respectively. Novel therapies, such as those employed to treat obesity-associated disease, including anti-diabetics, may prove successful at inhibiting aromatase specifically within the breast. This SpringerBrief will explore all of these issues in depth and the authors are in a unique position to write about this topic, having extensive experience in the field of aromatase research.​

Research on vitamin C and its effects on cancer is growing in popularity around the world as positive research continues to accumulate building a stronger case for its effectiveness. This concise SpringerBrief on Vitamin C and Cancer presents the latest findings on how vitamin C induces apoptosis. A high concentration of vitamin C allows for ascorbate to generate hydrogen peroxide in tissue that can selectively kill cancer cells. Research has confirmed that high-dose vitamin C is cytotoxic to a wide variety of cancer cell lines, and that it also boosts the anti-cancer activity of several common chemotherapy drugs. Vitamin C also does more than just kill cancer cells. It boosts immunity by stimulating collagen formation to help the body wall off the tumor. It inhibits hyaluronidase, an enzyme that tumors use to metastasize and invade other organs throughout the body. This concise and up-to-date Brief is geared towards cancer researchers and scientists, as well as physicians interested in the basic science and the translational potential of vitamin C in cancer therapeutics.

This SpringerBrief explores the physiological roles of Skp1-Cullin1-F-box Complex (SCF) and Anaphase Promoting Complex (APC) in normal cells and in tumor formation. These two related, multi-subunit E3 ubiquitin ligase enzymes, APC and SCF are thought to be the major driving forces governing proper cell cycle progression. Defective cell cycle regulation leads to genomic instability and ultimately, cancer development. Selective degradation of key cell cycle regulators by the ubiquitin-proteasome system has been proven to be a major regulatory mechanism for ensuring ordered and coordinated cell cycle progression. The SCF and APC E3 ligases have been characterized to play pivotal roles in regulating the cell cycle progression by timely degrading various critical cell cycle regulators. This Brief reviews recent studies that have shown that deregulation of signaling pathways in which the two ubiquitin ligases are involved causes aberrant cell cycle regulation, in turn leading to tumorigenesis. The text also discusses how SCF and APC may present promising therapeutic targets to treat various cancers.

A Quick Guide to Cancer Epidemiology is an ideal addition to Springer Briefs in Cancer Research. The Brief provides core concepts in cancer epidemiology and also gives a snapshot of the epidemiology of seventeen human cancers. The Brief aims to provide-with quantitative focus-estimates of the global burden of neoplasms, of recent and likely future trends, distribution, causes and strategies for prevention for major groups of cancers. Finally, the Brief will give an overview of severals factors that cause cancer including dietary factors, tobacco smoking, obesity and alcohol consumption.

This SpringerBrief gives the latest research on the role of miRNAs in breast cancer metastasis. MicroRNAs (miRNAs) are recently described small endogenous noncoding RNAs implicated in the posttranscriptional control of gene expression. These tiny molecules are involved in developmental, physiologic phenomenon as well as pathologic processes including cancers. In fact, miRNAs have emerged as critical regulators of cancer progression, invasion and metastasis. This is mainly because a single miRNA can affect several downstream genes and signaling pathways with oncogenic or tumor suppressor actions depending on the target genes affected. Due to this multimodal downstream signaling effects, these small endogenous molecules hold great promise in metastasis prevention and treatment. Modulating the activity of miRNAs can provide opportunities for novel cancer interventions. Targeting miRNAs could become a novel prognostic and therapeutic strategy to prevent the future development of metastasis. Thus, miRNAs could also serve as a potential targets for anti-metastatic therapy.   The book explores how the expression of miRNAs in the primary tumor could be silenced using antagomirs (chemically modified anti-miRNA oligonucleotides), which could prevent the development of metastasis; whereas once metastasis develops then it could be treated with miRNA mimics for inducing its expression for the treatment. Therefore, development of miRNA-based prophylactic therapies could serve as precision and personalized medicine against future development of metastasis of breast and other cancers.

This book provides up-to-date information on the development and progression of hepatocellular carcinoma (HCC) with a review of the cellular and molecular mechanisms involved in the disease process. Recent research in HCC has led to significant progress in our understanding of the cellular processes and molecular mechanisms that occur during multi-stage events that lead to hepatocarcinogenesis. The emergence of micro RNAs and molecular targeted therapies have added a new dimension in our efforts to combat this deadly disease, Chapters include discussion and evaluation of current intervention strategies and therapeutic options and a focus on the novel approaches that are being pursued, such as micro-RNA based therapies and personalized medicine to treat liver cancer. This book will be of interest to basic and clinical researchers, as well as to drug developers.

Abnormal expression of MHC class I molecules in malignant cells is a frequent occurrence that ranges from total loss of all class I antigens to partial loss of MHC specific haplotypes or alleles. Different mechanisms are described to be responsible for these alterations, requiring different therapeutic approaches. A complete characterization of these molecular defects is important for improvement of the strategies for the selection and follow-up of patients undergoing T-cell based cancer immunotherapy.  Precise identification of the mechanism leading to MHC class I defects  will help to develop new personalized patient-tailored treatment protocols. There is significant new research on the prevalence of various patterns of MHC class I defects and the underlying molecular mechanisms in different types of cancer. In contrast, few data is available on the changes in MHC class I expression during the course of cancer immunotherapy, but the authors have recently made discoveries that show the progression or regression of a tumor lesion in cancer patients undergoing immunotherapy depends on the molecular mechanism responsible for the MHC class I alteration and not on the type of immunotherapy used. According to this notion, the nature of the preexisting MHC class I lesion in the cancer cell has a crucial impact on determining the final outcome of cancer immunotherapy. This SpringerBrief will present how MHC class 1 is expressed, explain its role in tumor progression, and its role in resistance to immunotherapy. ​

This SpringerBrief is comprehensive account of the functions and effects of the Epstein-Barr virus (EBV) EBNA1 protein that relate to EBV-associated cancers and evidence for EBNA1 contributions to these cancers.   EBNA1 was the first EBV protein detected and the most critical for EBV latent infection. EBNA1 fulfills multiple functions at EBV genomes which have been described in many (sometimes confusing) reports over the last 28 years. While these were initially thought to be the only roles of EBNA1, many reports in recent years have shown that EBNA1 also directly affects cellular processes in ways that would be expected to contribute to oncogenesis. However, the degree to which EBNA1 promotes cell survival and oncogenesis in various types of human tumours is not entirely clear and a matter of debate. This book offers a current synopsis of EBNA1 functions in EBV latency, including functions in DNA replication, mitotic segregation and transcription. Mechanisms of these EBNA1 functions is also discussed as well as implications for tumourigenesis. In addition, the cellular effects of EBNA1 will be reviewed, including how EBNA1 manipulates specific cellular proteins and relationships to EBV-associated lymphomas and carcinomas.

Obesity is a risk factor for breast cancer in older women. A number of adipose-derived and obesity-related factors have been shown to affect tumour cell growth. These include adipokines, insulin, IGF-1 and oestrogens. The majority of obesity-related postmenopausal breast cancers are oestrogen-dependent. Since the ovaries no longer produce oestrogens after menopause, and that circulating levels are negligible, it is evident that it is the oestrogens produced locally within the breast adipose that are responsible for the increased growth of breast cancer cells. Aromatase is the enzyme that converts androgens into oestrogens and its regulation is dependent on the activity of a number of tissue-specific promoters. Targeting oestrogen biosynthesis in obesity may be useful for the prevention of breast cancer. Aromatase inhibitors are efficacious at treating postmenopausal breast cancer and recent studies suggest that they may also be useful in the prevention setting. However, these compounds inhibit the catalytic activity of aromatase and as a consequence lead to a number of undesirable side-effects, including arthralgia and possible cognitive defects due to inhibition of aromatase in the bone and brain, respectively. Novel therapies, such as those employed to treat obesity-associated disease, including anti-diabetics, may prove successful at inhibiting aromatase specifically within the breast. This SpringerBrief will explore all of these issues in depth and the authors are in a unique position to write about this topic, having extensive experience in the field of aromatase research.​

Research on vitamin C and its effects on cancer is growing in popularity around the world as positive research continues to accumulate building a stronger case for its effectiveness. This concise SpringerBrief on Vitamin C and Cancer presents the latest findings on how vitamin C induces apoptosis. A high concentration of vitamin C allows for ascorbate to generate hydrogen peroxide in tissue that can selectively kill cancer cells. Research has confirmed that high-dose vitamin C is cytotoxic to a wide variety of cancer cell lines, and that it also boosts the anti-cancer activity of several common chemotherapy drugs. Vitamin C also does more than just kill cancer cells. It boosts immunity by stimulating collagen formation to help the body wall off the tumor. It inhibits hyaluronidase, an enzyme that tumors use to metastasize and invade other organs throughout the body. This concise and up-to-date Brief is geared towards cancer researchers and scientists, as well as physicians interested in the basic science and the translational potential of vitamin C in cancer therapeutics.

This SpringerBrief explores the physiological roles of Skp1-Cullin1-F-box Complex (SCF) and Anaphase Promoting Complex (APC) in normal cells and in tumor formation. These two related, multi-subunit E3 ubiquitin ligase enzymes, APC and SCF are thought to be the major driving forces governing proper cell cycle progression. Defective cell cycle regulation leads to genomic instability and ultimately, cancer development. Selective degradation of key cell cycle regulators by the ubiquitin-proteasome system has been proven to be a major regulatory mechanism for ensuring ordered and coordinated cell cycle progression. The SCF and APC E3 ligases have been characterized to play pivotal roles in regulating the cell cycle progression by timely degrading various critical cell cycle regulators. This Brief reviews recent studies that have shown that deregulation of signaling pathways in which the two ubiquitin ligases are involved causes aberrant cell cycle regulation, in turn leading to tumorigenesis. The text also discusses how SCF and APC may present promising therapeutic targets to treat various cancers.

A Quick Guide to Cancer Epidemiology is an ideal addition to Springer Briefs in Cancer Research. The Brief provides core concepts in cancer epidemiology and also gives a snapshot of the epidemiology of seventeen human cancers. The Brief aims to provide-with quantitative focus-estimates of the global burden of neoplasms, of recent and likely future trends, distribution, causes and strategies for prevention for major groups of cancers. Finally, the Brief will give an overview of severals factors that cause cancer including dietary factors, tobacco smoking, obesity and alcohol consumption.

This SpringerBrief gives the latest research on the role of miRNAs in breast cancer metastasis. MicroRNAs (miRNAs) are recently described small endogenous noncoding RNAs implicated in the posttranscriptional control of gene expression. These tiny molecules are involved in developmental, physiologic phenomenon as well as pathologic processes including cancers. In fact, miRNAs have emerged as critical regulators of cancer progression, invasion and metastasis. This is mainly because a single miRNA can affect several downstream genes and signaling pathways with oncogenic or tumor suppressor actions depending on the target genes affected. Due to this multimodal downstream signaling effects, these small endogenous molecules hold great promise in metastasis prevention and treatment. Modulating the activity of miRNAs can provide opportunities for novel cancer interventions. Targeting miRNAs could become a novel prognostic and therapeutic strategy to prevent the future development of metastasis. Thus, miRNAs could also serve as a potential targets for anti-metastatic therapy.   The book explores how the expression of miRNAs in the primary tumor could be silenced using antagomirs (chemically modified anti-miRNA oligonucleotides), which could prevent the development of metastasis; whereas once metastasis develops then it could be treated with miRNA mimics for inducing its expression for the treatment. Therefore, development of miRNA-based prophylactic therapies could serve as precision and personalized medicine against future development of metastasis of breast and other cancers.

This book provides up-to-date information on the development and progression of hepatocellular carcinoma (HCC) with a review of the cellular and molecular mechanisms involved in the disease process. Recent research in HCC has led to significant progress in our understanding of the cellular processes and molecular mechanisms that occur during multi-stage events that lead to hepatocarcinogenesis. The emergence of micro RNAs and molecular targeted therapies have added a new dimension in our efforts to combat this deadly disease, Chapters include discussion and evaluation of current intervention strategies and therapeutic options and a focus on the novel approaches that are being pursued, such as micro-RNA based therapies and personalized medicine to treat liver cancer. This book will be of interest to basic and clinical researchers, as well as to drug developers.