Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications.
Animals ; Antineoplastic Agents ; therapeutic use ; Basal Cell Nevus Syndrome ; drug therapy ; metabolism ; Carcinoma, Basal Cell ; drug therapy ; metabolism ; Cell Differentiation ; Cerebellar Neoplasms ; drug therapy ; metabolism ; Hedgehog Proteins ; antagonists & inhibitors ; metabolism ; Humans ; Medulloblastoma ; drug therapy ; metabolism ; Models, Animal ; Neoplasms ; drug therapy ; metabolism ; Patched Receptors ; Receptors, Cell Surface ; genetics ; metabolism ; Signal Transduction ; drug effects ; Skin Neoplasms ; drug therapy ; metabolism

We report a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. The patient demonstrated a round mass in the right occipital area for 12 months and the lesion grew rapidly to assume 8x6.5x4cm in diameter, with areas of superficial erosion and crusting within the recent 3 months. The entire lesion was removed with a wide surgical excision. It recurred on the neck area 4 months after excision and the lesion was removed with surgical resection again. There was evidence of multiple metastases on CNS and mediastinal lymph nodes after 6 months. The patient was treated with cisplatin and etoposide combination chemotherapy and a partial response was achieved.
Adult ; Antineoplastic Agents, Combined/administration & dosage ; Biopsy, Needle ; Brain Neoplasms/therapy ; Brain Neoplasms/secondary* ; Brain Neoplasms/pathology ; Case Report ; Combined Modality Therapy ; Follow-Up Studies ; Head and Neck Neoplasms/therapy ; Head and Neck Neoplasms/surgery ; Head and Neck Neoplasms/pathology* ; Human ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Neoplasms, Basal Cell/therapy ; Neoplasms, Basal Cell/secondary* ; Neurosurgical Procedures/methods ; Reoperation ; Scalp* ; Skin Neoplasms/therapy ; Skin Neoplasms/surgery ; Skin Neoplasms/pathology* ; Tomography, X-Ray Computed

PURPOSE: This study was conducted to investigate the neurocognitive functioning of children with intracranial germ cell tumor (IGCT) prior to receiving proton beam therapy (PBT), and to identify differential characteristics of their neurocognitive functioning depending on tumor location. As a secondary object of this study, neurocognitive functions were followed up at 1-2 years after PBT to examine early post-treatment changes. MATERIALS AND METHODS: Between 2008 and 2014, 34 childrenwith IGCT treatedwho received PBT atNational Cancer Center, Korea were enrolled in this study. Standardized neurocognitive tests of intelligence, memory, and executive functioning were performed with baseline psychological assessments using the Child Behavior Checklist (CBCL). Follow-up assessments after PBT were conducted in 20 patients (T2). The results were analyzed based on the locations of tumors, which included the suprasellar, pineal gland, basal ganglia, and bifocal regions. RESULTS: The neurocognitive function of IGCT patients was significantly lower than that of the normal population in performance intelligence quotient (p=0.041), processing speed (p=0.007), memory (p < 0.001), and executive functioning (p=0.010). Patients with basal ganglia tumors had significantly lower scores for most domains of neurocognitive functioning and higher scores for CBCL than both the normal population and patients with IGCT in other locations. There was no significant change in neurocognitive function between T1 and T2 for all types of IGCT patients in first 1-2 years after PBT. CONCLUSION: Tumor location significantly affects the neuropsychological functioning in patients with IGCT. Neuropsychological functioning should be closely monitored from the time of diagnosis in IGCT patients.
Basal Ganglia ; Brain Neoplasms ; Checklist ; Child Behavior ; Child* ; Cognition ; Diagnosis ; Follow-Up Studies ; Germ Cells* ; Humans ; Intelligence ; Korea ; Memory ; Neoplasms, Germ Cell and Embryonal* ; Pineal Gland ; Proton Therapy

We herein present the case of a 55-year-old woman with a previous history of malignancies--uterine adenocarcinoma, basal cell carcinoma (which occurred twice consecutively), recurrent respiratory infections due to common variable immunodeficiency (CVID), and systemic granulomatous disease diagnosed at a later age. The patient suffered from diffuse large B cell lymphoma (DLBCL), which was successfully treated with R-CHOP chemotherapy, and continued with immunoglobulin supplementation. The patient was free of lymphoma and infectious complications for over 20 months despite her persistent immunodeficiency, but eventually developed colorectal adenocarcinoma. To the best of our knowledge, this is the first reported case of CVID associated with multiple solid tumours and DLBCL.
Adenocarcinoma ; etiology ; Carcinoma, Basal Cell ; etiology ; Common Variable Immunodeficiency ; complications ; diagnosis ; therapy ; Fatal Outcome ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; etiology ; Middle Aged ; Neoplasms, Multiple Primary ; etiology ; pathology ; therapy ; Respiratory Tract Infections ; etiology ; Skin Neoplasms ; etiology ; Uterine Neoplasms ; etiology

The multifactorial etiology of BCC(basal cell carcinoma) are incompletely understood, including factors leading to multiple lesions in some patients. Cases of multiple BCCs reported in the literature have been associated with UV irradiation, inorganic arsenic poisoning, X-ray therapy, hematologic malignancy and several genodermatoses such as nevoid BCC syndrome, albinism, xeroderma pigmentosum. Multiple BCCs presented on the sun-protected areas, lacking predisposing risk factors which have been known, is rare skin condition. However, it suggests that there may be an unknown genetic susceptibility to the development of multiple BCCs. We report a rare case of multiple BCCs, which had developed only on the sun-protected areas in 64-year-old man, without any known predisposing causes.
Albinism ; Arsenic Poisoning ; Carcinoma, Basal Cell* ; Genetic Predisposition to Disease ; Hematologic Neoplasms ; Humans ; Middle Aged ; Risk Factors ; Skin ; X-Ray Therapy ; Xeroderma Pigmentosum

The clinicopathological findings in 9 patients with germ cell tumors originating in the basal ganglia and thalamus are presented. The incidence of germ cell tumors of the basal ganglia and thalamus was 16.4% of all 55 cases of primary intracranial germ cell tumors. These included 6 cases of germinomas and 3 cases of malignant mixed germ cell tumors(MGCT). The average age at diagnosis was 16.9 years(range 9.5-39 years). The sex incidence showed male dominance(8:1). The clinical course of germinoma in the basal ganglia and thalamus was slowly progressive and the average duration of symptoms before diagnosis was 29 months. The most common symptom and sign was hemiparesis and which was not normalized in all cases in spite of complete response to irradiation or chemotherapy. In case of germinomas, symptoms of increased intracranial pressure were found in only 1 case. Germinomas in the basal ganglia and thalamus had characteristic radiological findings different from that of pineal or suprasellar germinomas : irregular mixed density or signals. Therapy consisted of stereotactic biopsy and irradiation in 6 cases, subtotal removal followed by irradiation and chemotherapy in 1 case, irradiation alone in 1 case and chemotherapy alone in 1 case. Of the 6 patients with germinoma, 5 are alive and disease free for 5 to 111 months after diagnosis(mean 57 months, median 62 months), but one patient died of recurrence on the primary site, temporal lobe, and cerebellum 87 months after cranial irradiation. Only 1 of 3 patients with malignant MGCT is still living 6 months after diagnosis, he showed complete response to chemotherapy and is now under maintenance of chemotherapy. There was no recovery of hemiparesis in patient with advanced germinoma in this region, early detection and treatment on the basis of biopsy, radiological findings and tumor marker study are essential in the management of germ cell tumors originating in the basal ganglia and thalamus.
Basal Ganglia* ; Biopsy ; Cerebellum ; Cranial Irradiation ; Diagnosis ; Drug Therapy ; Germ Cells* ; Germinoma ; Humans ; Incidence ; Intracranial Pressure ; Male ; Neoplasms, Germ Cell and Embryonal* ; Paresis ; Recurrence ; Temporal Lobe ; Thalamus*

OBJECTIVETo use partial differential -aminolevulinic acid induced photodynamic therapy (ALA-PDT) increasingly in treating skin cancers and other diseases in many countries and to explore the efficacy of ALA-PDT for skin cancers in China.

METHODSEighty-eight patients, including 34 cases of basal cell carcinoma (BCC), 32 cases of squamous cell carcinoma (SCC), two cases of basal-squamous cell carcinoma (BSCC), one case of verrucuous carcinoma, nine cases of Bowen disease, two cases Paget disease of the nipple and eight cases of extramammary Paget disease, were treated by the partial differential alpha-aminolevulinic acid induced photodynamic therapy first in China from 1997 to 2000.

RESULTSAll BCC, including 11 cases of superficial lesions and 29 solid lesions, achieved complete reaction (CR) by 1-4 times of the ALA-PDT. Except one patient with adenoid SCC (grade III), all SCC (grade I and grade II) patients achieved complete remission by 3-6 times of ALA-PDT. All Bowen diseases achieved complete reaction by 1-4 times. Although for Paget diseases it could not cure the disease simply by ALA-PDT, it could control the symptoms. The recurrence rates were 11% (4/34) for BCC, and 22% (7/32) for SCC by following up 1-3 years after the therapy. The continuous therapy is still effective.

CONCLUSIONSALA-PDT is an effective, non-traumatic treatment for patients with BCC, SCC, Bowen and Paget diseases. It is especially suitable for older and weaker patients or those who are not tolerable to other therapies. It also has a unique advantage for tumors in specific anatomical areas. It is a new alternative modality for skin cancer therapies.

Adult ; Aged ; Aminolevulinic Acid ; therapeutic use ; Carcinoma, Basal Cell ; drug therapy ; Carcinoma, Squamous Cell ; drug therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Photochemotherapy ; adverse effects ; Skin Neoplasms ; drug therapy

Central nervous system germ cell tumor is a rare but important tumor in childhood brain tumors. It requires a multidisciplinary approach to increase survival and promote quality of life, and all three treatment modalities including surgery, radiotherapy and chemotherapy has its own distinct role for germ cell tumor. For germinoma, radiotherapy alone can cure the disease but, the effort to limit the long term toxicity and the proper combination of chemotherapy and radiotherapy are under investigation. Craniospinal irradiation is reserved only for the disseminated germinoma or nongerminomatous germ cell tumor (NGGCT). For germinoma, craniospinal irradiation of 20 to 24 Gy is sufficient to control microscopic disease in the spinal axis. Chemotherapy and radiotherapy composed of 30 to 40 Gy of local field radiotherapy and 20 to 24 Gy of whole ventricular irradiation are required for localized germinoma, but the proper combination of two modalities has yet to be defined. For NGGCT, both the chemotherapy and radiotherapy should be performed, and survival rate is substantially increasing with modern treatment protocols. The omission of craniospinal irradiation is being tried for the localized NGGCT in international cooperative group trials. Surgery has its role for the resection of residual disease after the treatment, and the extent of resection in NGGCT has the prognostic implication. Bifocal germ cell tumors and basal ganglia germ cell tumor have distinctive clinical course and mandate special attention. To advance clinical and biological perspectives in central nervous germ cell tumor, the cooperation and communication of the multidisciplinary specialists are essential.
Axis, Cervical Vertebra ; Basal Ganglia ; Brain Neoplasms ; Central Nervous System ; Clinical Protocols ; Craniospinal Irradiation ; Drug Therapy ; Germ Cells ; Germinoma ; Neoplasms, Germ Cell and Embryonal ; Quality of Life ; Radiotherapy ; Specialization ; Survival Rate

BACKGROUND: Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, symptoms of hypothalamic dysfunction, and seizures. It commonly precedes the diagnosis of cancer. Small-cell lung cancer is the neoplasm that is most frequently reported as the etiology underlying PLE. CASE REPORT: This report describes a male patient who presented with neurologic symptoms consistent with anterograde amnesia, apathy, and disorientation. MRI revealed diffuse hyperintensities located predominantly in the medial bitemporal lobes, basal ganglia, frontal lobes, and leptomeninges on fluid attenuated inversion recovery images, suggesting PLE. Study of the primary tumor revealed squamous cell carcinoma of the lung. The patient was treated with neoadjuvant chemotherapy followed by surgery and adjuvant chemoradiotherapy, which resulted in his neurologic symptoms gradually improving. CONCLUSIONS: PLE might be a rare debut of squamous cell carcinoma of the lung. Treatment of the primary tumor may improve the neurologic symptoms.
Amnesia, Anterograde ; Apathy ; Basal Ganglia ; Carcinoma, Squamous Cell* ; Chemoradiotherapy, Adjuvant ; Diagnosis ; Drug Therapy ; Frontal Lobe ; Humans ; Limbic Encephalitis* ; Lung Neoplasms ; Lung* ; Magnetic Resonance Imaging ; Male ; Memory ; Neurologic Manifestations ; Paraneoplastic Syndromes ; Seizures

Primary intracranial germ cell tumors(GCTs) are relatively rare brain tumors that show a diverse range of histologic features from benign to highly malignant conditions. To determine their clinical findings, pathology, treatment and outcome, we analyzed the medical records of 45 patients with primary intracranial GCTs treated at our hospital between June 1989 and December 1996. Thirty-two were males and 13 were females, and their ages ranged from three to 43 years. Fifteen cases were located in the pineal region and 13 in the suprasellar. The remaining locations were the basal ganglia in eight cases, both the pineal and suprasellar region in five, and others in four. In the pineal region, there was a male predominance(13:2), but in the suprasellar region, more cases(ten of 13) involved females. Of the 15 patients with tumors of the pineal region, increased intracranial pressure(IICP) was evident in 12 and six had Parinaud's syndrome. Of the 13 patients with tumors of suprasellar region, nine had diabetes insipidus; seven, visual deficit; and six, hypopituitarism. Germinoma was the most common histologic type. Other types of histology were two teratomas, three embryonal carcinomas, one endodermal sinus tumor, one choriocarcinoma, and five mixed GCTs. All patients except those with a teratoma underwent whole craniospinal irradiation. We performed gross total or subtotal removal in cases of non-germinomatous GCTs(NGGCTs) and mixed tumors, but biopsy or partial removal was preferred for the germinomas. Thirteen of 45 patients received adjuvant chemotherapy. All malignant NGGCT and mixed tumor patients were treated with adjuvant chemotherapy, as well as three of 33 germinoma patients. Three of five malignant NGGCT patients and two of five mixed tumor patients died of tumor progression. Two of 33 germinoma patients died not of disease progression but of other causes. Actuarial survival records showed that overall two-year and five-year survival rates were 89.9% and 71.9%, respectively. There were no statistically significant differences with regard to patient's age, sex, or tumor location. With regard to their histology and surgical extent, malignant NGGCTs and mixed tumors showed statistically significant differences. Five-year surival rates of germinoma and malignant NGGCT patients were 83.1% and 53.3%, respectively. We suppose that the appropriate combination of chemotherapy and surgery, with or without radiation therapy, remains to be defined, and that to determine the appropriate management protocol for malignant NGGCTs and mixed tumors, larger series of patients must be analyzed.
Basal Ganglia ; Biopsy ; Brain Neoplasms ; Carcinoma, Embryonal ; Chemotherapy, Adjuvant ; Choriocarcinoma ; Craniospinal Irradiation ; Diabetes Insipidus ; Disease Progression ; Drug Therapy ; Endodermal Sinus Tumor ; Female ; Germ Cells* ; Germinoma ; Humans ; Hypopituitarism ; Male ; Medical Records ; Neoplasms, Germ Cell and Embryonal* ; Ocular Motility Disorders ; Pathology ; Pregnancy ; Survival Rate ; Teratoma