Intracranial germ cell tumors (iGCTs) are a heterogeneous group of tumors with peculiar characteristics clearly distinguished from other brain tumors of neuroepithelial origin. Diverse histology, similarity to gonadal GCT, predilection to one sex, and geographic difference in incidence all present enigmas and fascinating challenges. The treatment of iGCT has advanced for germinoma to date; thus, clinical attention has shifted from survival to long-term quality of life. However, for non-germinomatous GCT, current protocols provide only modest improvement and more innovative therapies are needed. Recently, next-generation sequencing studies have revealed the genomic landscape of iGCT. Novel mutations in the KIT-RAS-MAPK and AKT-MTOR pathways were identified. More importantly, methylation profiling revealed a new method to assess the pathogenesis of iGCT. Molecular research will unleash new knowledge on the origin of iGCT and solve the many mysteries that have lingered on this peculiar neoplasm for a long time.
Brain Neoplasms ; Germ Cells ; Germinoma ; Gonads ; Incidence ; Methods ; Methylation ; Neoplasms, Germ Cell and Embryonal ; Quality of Life ; Therapies, Investigational

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit.We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.
Antineoplastic Agents ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Humans ; Medication Therapy Management ; Molecular Targeted Therapy ; adverse effects ; methods ; Neoplasms ; drug therapy ; genetics ; Pharmacogenomic Testing ; Therapies, Investigational ; methods

Intestinal hypoganglionosis is a rare innervation disorder that provides numerous nutritional, medical and surgical challenges. In this case report, we present a case of a newborn with intestinal hypoganglionosis leading to intestinal failure and intestinal failure-associated liver disease who responded to Omegaven™, a fat emulsion comprised of omega-3 fatty acids. Omegaven™ has been shown to be beneficial in the management of cholestatic liver injury. Clinical success with Omegaven™ was seen in this patient with a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and complete resolution of cholestasis with a direct bilirubin of zero within two weeks of initiation of Omegaven™. No current guidelines for the diagnosis and management of hypoganglionosis are available. We recommend a multidisciplinary approach and the use of novel therapies such as fat emulsions composed of omega-3 fatty acids for improved patient outcomes. Appropriate compassionate use protocols should be obtained from the Food and Drug Administration prior to initiation of Omegaven™.
Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Bilirubin ; Cholestasis ; Compassionate Use Trials* ; Diagnosis ; Empathy* ; Emulsions ; Fatty Acids, Omega-3 ; Hirschsprung Disease ; Humans ; Infant, Newborn ; Liver ; Liver Diseases ; Parenteral Nutrition, Total ; United States Food and Drug Administration

Thyroid ophthalmopathy (TO) is an autoimmune inflammatory disorder involving the orbit characterized by inflammation and swelling of the extraocular muscles and an increase in orbital fat and connective tissue. Despite extensive research, TO continues to be a difficult condition for the patient to cope with and for the clinician to treat. Current treatments consist of systemic immunosuppression, orbital irradiation, and surgery. It is promising for patient refractory to conventional therapy that pathogenesis of TO at molecular level which advance development of new therapies targeting cellular immunity are now better understood. Future therapies targeting immune system or specific molecules are under investigation and show promise for the future. This review will describe current trends in the management of TO, from well-established therapies such as glucocorticoids, orbital irradiation and orbital decompression to more innovative therapies targeting immune system or specific molecules involved in TO pathogenesis.
Adrenal Cortex Hormones ; Connective Tissue ; Decompression ; Glucocorticoids ; Humans ; Immune System ; Immunity, Cellular ; Immunosuppression ; Inflammation ; Muscles ; Orbit ; Therapies, Investigational ; Thyroid Gland*

Retinoblastoma is a rare disease, but most common tumor which arises in eye. It can affect one or both eyes, and the main pathophysiology is explained by the "Two-hit theory" - the germline mutation of the RB1 gene. Most common clinical symptoms are leuocoria, strabismus, poor visual tracking, glaucoma, and orbital cellulitis. Diagnosis is made by ophthalmologist through fundoscopic examination; Examination under General Anesthesia (EUA) is recommended until the age 3. Orbital CT and MRI can detect the tumor invasion on optic nerve, central nervous system. CSF studies, examination of bone is helpful if the distant metastasis is suspected. Biopsy is rarely done unless in the case of enucleation. Enucleated eye should be explored for the invasion to the optic nerve, choroid, anterior chamber, iris and pupil. Treatment strategies can be different according to the disease status. If the single eye is involved, the treatment goal will be the removal of tumor and prevention of relapse. Local therapies include cryotherapy, laser photocoagulation, thermotherapy can be the choice, and if the tumor is too large for the local therapy, enucleation should be concerned. Nowadays, chemo-reduction combined with local therapy, intra-arterial and intravitreous chemotherapeutic agent injections are studied to avoid enucleation. In bilateral retinoblastoma, multidisciplinary treatments include chemoreduction, external beam radiotherapy, local therapy and other experimental therapies are needed: like intra-arterial injection, intra-vitreal injection, and high-dose chemotherapy with autologous stem cell transplantation. Early detection of retinoblastoma is important to save the vision and eyeball.
Anesthesia, General ; Anterior Chamber ; Biopsy ; Central Nervous System ; Choroid ; Cryotherapy ; Diagnosis ; Drug Therapy ; Eye Enucleation ; Germ-Line Mutation ; Glaucoma ; Hyperthermia, Induced ; Injections, Intra-Arterial ; Intravitreal Injections ; Iris ; Light Coagulation ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Optic Nerve ; Orbit ; Orbital Cellulitis ; Pupil ; Radiotherapy ; Rare Diseases ; Recurrence ; Retinoblastoma ; Stem Cell Transplantation ; Strabismus ; Therapies, Investigational

OBJECTIVETo review the experimental drugs for the treatment of autoimmune myocarditis.

DATA SOURCESThe literatures published in English about different kinds of experimental drugs based on different therapeutic mechanisms for the treatment of autoimmune myocarditis were obtained from PubMed from 2002 to 2013.

STUDY SELECTIONOriginal articles regarding the experimental drugs for treatment of autoimmune myocarditis were selected.

RESULTSThis study summarized the effects of the experimental drugs for the treatment of autoimmune myocarditis, such as immunomodulators and immunosuppressants, antibiotics, Chinese medicinal herbs, cardiovascular diseases treatment drugs, etc. These drugs can significantly attenuate autoimmune myocarditis-induced inflammation and fibrosis, alleviate autoimmune myocarditis-triggered overt lymphocyte proliferation, and meanwhile reduce Th1 cytokines (IFN-γ and IL-2) and increase Th2 cytokines (IL-4 and IL-10).

CONCLUSIONThis study summarized recent advances in autoimmune myocarditis treatment and further proposes that traditional Chinese medicine and immune regulators will play important roles in the future.

Animals ; Autoimmune Diseases ; drug therapy ; Drugs, Investigational ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Myocarditis ; drug therapy ; Therapies, Investigational ; trends

Tea polyphenols (TPs), major biological active constituents of green tea, exert moderate and selective anticancer effects. Molecular mechanisms of TPs in cancer prevention and treatment involve multiple potential molecular targets. TPs inhibit growth factor receptor-mediated signal transduction pathway, decrease the activities of mitogen activated protein kinases and activator protein transcription factor-1, block nuclear factor-kappaB signaling pathway, reduce proteasome activity, lower overexpression of COX-2, subside dihydrofolate reductase and telomerase, and inhibit DNA methylation and matrix metalloproteinases. Furthermore, TPs enhance the inhibitory effect on the growth of cancers by traditional anticancer drugs or targeted antitumor drugs in vitro and in vivo and reverse multidrug resistances of cancer cells to vincristine, doxorubicin, and 5-fluorouracil. Besides, TPs reduce the nephrotoxicity induced by cisplatin, ameliorate irinotecan-induced side effects in the small intestine of mice, and decrease bleomycin-caused DNA damage in human leukocytes. TPs also increase antitumor activity of vaccine through immunological modulation. TPs play roles of the augmentation of antitumor effects, the reversal of multidrug resistance, and the reduction of side effects of chemotherapeutic drugs. TPs could be used as biochemical modulators in cancer therapy.
Animals ; Antineoplastic Agents ; isolation & purification ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; drug therapy ; Polyphenols ; isolation & purification ; pharmacology ; Signal Transduction ; drug effects ; Tea ; chemistry ; Therapies, Investigational

PURPOSE: We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. METHODS: We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. RESULTS: A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was 44.4%+/-16.6% and disease status at the time of HDCT/autoPBSCT tended to influence survival (57.1%+/-18.7% of cases with CR vs. 0% of cases with non-CR, P=0.07). CONCLUSION: Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment.
Adolescent ; Child ; Disease-Free Survival ; Humans ; Korea ; Male ; Neoplasm Metastasis ; Peripheral Blood Stem Cell Transplantation ; Pilot Projects ; Retrospective Studies ; Sarcoma, Ewing ; Stem Cell Transplantation ; Therapies, Investigational

The healthcare for elite athletes has the potential to create many ethical issues for sports practitioners. And the relationship between a sports practitioner and an athlete differs significantly from the traditional doctor-patient relationship. However, there has been little discussion of them to date. To investigate the ethical awareness and concerns in sports medicine field, we surveyed the responses of Korean medical team to a questionnaire during the Summer Olympic Games 2012. The questionnaire was developed to access a wide-range of common ethical issues in sports medicine; conflict of interests, confidentiality, pediatric athletes, performance-enhancing substances, infectious disease, innovative therapies, medical advertising. Twenty-nine out of 32 sports practitioners responded to the questionnaire (90.6%). Respondents identified many ethical matters concerning the unique characteristics of athletes-as-patients in sports medicine. This study has started the process of identifying contemporary ethical problems with regard to the sports medicine, and there should be further studies dealing with these problems.
Athletes ; Communicable Diseases ; Confidentiality ; Conflict of Interest ; Delivery of Health Care ; Humans ; Performance-Enhancing Substances ; Surveys and Questionnaires ; Sports ; Sports Medicine ; Therapies, Investigational

OBJECTIVE/strong: To present a rare case of maxillary swelling; its investigation and management.br /br /strongMETHODS/strong:br /strongDesign/strong: Case Report br /strongSetting/strong: Tertiary Government Teaching Hospital br /strongPatient/strong: One br /br /strongRESULTS/strong: A 45-year-old female presented with a right maxillary swelling of six months duration. Radiological investigation revealed a radiolucent lesion arising from the inferior aspect of the right maxilla with no areas of calcification. Incisional biopsy report was consistent with giant cell tumor. The mass was excised via a Weber Ferguson incision under general anesthesia.CONCLUSION/strong: Though rare, giant cell tumor should be considered as one of the differential diagnosis in cases of maxillary swelling. Adequate surgical excision with long-term follow-up should be the treatment of choice for managing a giant cell lesion of the maxilla./p
Human ; Female ; Middle Aged ; Giant Cell Tumors-diagnosis ; neoplasms ; Maxilla ; Therapies, Investigational ; Tomography Scanners, X-Ray Computed