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At least 19 recordsLinked to original sources
PubMed2026

Tumoral switch in NUMB splicing changes essential transcription pathways and induces malignant properties in tumour cells.

BACKGROUND: Emerging evidence indicates that cancer is associated with widespread splicing alterations that generate tumour-specific isoforms. One example is NUMB, an evolutionarily conserved adaptor protein, which produces four isoforms (p72, p71, p66, and p65) through alternative splicing of exons 3 and 9. Although traditionally considered as a tumour suppressor, NUMB has also been reported as an oncogene. We propose that this dual role reflects isoform-specific expression. RESULTS: Using public databases, we identify a tumour-associated switch in NUMB isoform expression: p72 and p71 are upregulated in tumours, whereas p66 and p65 are more highly expressed in non-tumour tissues. These isoforms show distinct associations with key cellular processes. NUMBL, a NUMB homolog, displays expression patterns similar to p65. We further identify two transcriptional clusters: one characterised by high expression of p72 and p71, and the other by enhanced p66/p65/NUMBL expression. These clusters exhibit differential associations with Notch, WNT/β-catenin, Hedgehog, and Hippo signalling pathways, suggesting isoform-specific regulatory roles. In breast cancer cell lines, we develop a NUMB-score based on isoform expression, which classifies cell lines into biologically distinct groups. The p72/p71-enriched group shows distinct signatures, pathway activity, and drug sensitivity. Application of this score to TCGA-BRCA samples reveals a significant link between high NUMB-score and poor survival, as confirmed by Kaplan-Meier analysis. CONCLUSIONS: We find that NUMB emerges as a potential oncogenic contributor and biomarker in the context of splicing-based precision oncology, highlighting Isoform-specific expression as a clinical determinant of tumour behaviour, pathway activity, and therapeutic response.

Humans↗
PubMed1989

[Analysis of subjective symptoms of coldness and numbness in the upper and lower limbs among patients with vibration syndrome].

Coldness and numbness of the lower limbs in patients with vibration syndrome were studied in correlation with the frequency of attacks of vibration-induced white finger (VWF), coldness and numbness of the upper limbs, and awakening at night due to numbness of the arm. Subjects were 229 patients aged 50-69 years without disease other than vibration syndrome who had mainly operated chain saws. The present study showed that patients with more frequent VWF attacks had a higher prevalence and frequency of coldness in the fingers, awakening at night due to numbness of the arm, and coldness and numbness in the legs. Particularly patients having almost daily attacks of VWF had a high prevalence of these symptoms. Positive correlation was observed in prevalence and frequency between coldness of the fingers and that of the legs, and between coldness and numbness in the legs. The prevalence of VWF, numbness and coldness of the fingers, and coldness of the legs was higher the longer the total chain saw operating period. The present findings suggest that patients with severe circulatory disturbances in the upper limbs have severe circulatory disturbance in the lower limbs. Further studies on circulatory disturbances in the lower limbs are indicated, and their mechanism involved should be also pursued from the pathogenetic point of view.

Aged↗
PubMed1989

numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos.

Neurons and support cells of each sensory organ in Drosophila embryos are most likely derived from a single precursor cell. This cell lineage is affected in numb mutants. Morphological alterations of sensory structures, as well as changes in the number of cells expressing cell type-specific markers, indicate that sensory neurons in numb mutant embryos are transformed into lineage-related nonneuronal support cells. Thus the numb gene controls the fate of progeny derived from sensory organ precursors. The numb gene has been isolated by the plasmid rescue method. The structure of its predicted product is discussed.

Amino Acid Sequence↗
PubMed1991

The numb chin.

An apparently innocuous complaint such as a numb chin may be associated with malignant disease, either as heralding symptom or as a manifestation of metastasis. A series of 15 patients with numbness of the chin is presented in which a malignancy was diagnosed prior to the numbness. The numbness diminished or disappeared in 66% of the patients following either systemic chemotherapy or radiotherapy.

Adolescent↗
PubMed1987

Nasal tip numbness following rhinoplasty.

Inquiry into the sensory changes of the nasal tip following rhinoplasty in 75 patients showed that 65.3% experienced some degree of numbness of the nasal tip after operation. This included 29.3% who reported numbness as the only sensory change. The numbness lasted less than 3 months in 68.3% of the latter cases. Rhinoplasty involving tip reduction in particular was likely to result in postoperative numbness.

Humans↗
PubMed1991

The "numb cheek-limp lower lid" syndrome.

A patient developed isolated numbness, 1st confined to the lateral nose and upper lip, but later involving the cheek, lower lip, upper gingiva, and the palate. This numbness was later associated with paresis of the muscles of the upper lip and angle of the mouth and with ipsilateral lower lid droop (the "numb cheek-limp lower lid" syndrome). Squamous cell carcinoma was discovered infiltrating the infraorbital nerve and distal branches of the facial nerve. Cheek numbness associated with lower eyelid or upper lip weakness may herald a neoplasm affecting the infraorbital nerve and distal facial nerve branches.

Aged↗
PubMed1986

The numb cheek syndrome: a sign of infraorbital neuropathy.

Three patients with skin cancer had numbness isolated to one cheek, in the distribution of the infraorbital nerve. Hypesthesia also involved the medial and lateral upper incisors and canine teeth, and adjacent gingiva, sparing the more posterior teeth and gums. The molar and premolar teeth and gums are innervated by the posterior and middle superior alveolar nerves; because these structures were spared, the pathologic process was localized to the infraorbital foramen, and we could exclude involvement of the maxillary division more proximally. In two patients, cheek numbness heralded recurrent squamous cell carcinoma. Analogous anatomy at the mental foramen should help distinguish intracranial leptomeningeal from local mandibular lesions producing isolated numbness of the chin.

Aged↗
PubMed1992

[A case of spontaneous mediastinal emphysema developed by numbness of the left arm, dysphagia and chest pain].

A 20-year-old female developed dysphagia, chest pain and numbness of the left arm after dinner on August 22, 1990. She consulted a doctor, who diagnosed tachycardia and prescribed propranolol. On August 23, she hadn't improved. On the same day, she visited our hospital. Chest X-ray films revealed lucent band and distinct line running parallel to the border of the heart and we suspected mediastinal emphysema. Immediately we took chest CT scan, which demonstrated free air surrounding the trachea, thoracic aorta and heart. We diagnosed spontaneous mediastinal emphysema. She was treated with bed rest and mediastinal emphysema subsided within 8 days. The numbness in the patient's arm is an unusual symptom in mediastinal emphysema. We suggest that the numbness of the arm may be due to interference with the circulation to the arm by distention of the mediastinal tissue.

Adult↗
PubMed1990

Numb chin syndrome: a case report.

Neuropathy of the inferior alveolar nerve is common in dental practice. Its cause, when not a result of local anesthetic, is normally from dental disease or trauma. Isolated mental neuropathy (numb chin syndrome) is extremely uncommon, and its most common cause also is dental. The next most common cause is from an underlying neoplasm, and some cases have resulted from systemic disease (eg, multiple sclerosis). Some patients show no evidence of additional disease and experience spontaneous remission of the symptom. Numb chin syndrome cases require coordination of treatment between dentists and physicians. Since a disproportionate number of these cases present with a numb chin as the first symptom of a neoplasm, aggressive diagnosis is required. Careful follow up is important before dismissing it as a spontaneous remission. Dentists must be familiar with isolated mental neuropathy and its medical implications because they are likely to be the first health professionals that patients present to for diagnosis.

Adult↗
PubMed1987

Facial numbness and dysesthesia. New features of carotid artery dissection.

Facial numbness and dysesthesia have not been emphasized as presenting features in spontaneous internal carotid artery dissection. Progressive facial pain, accompanied by oculosympathetic paresis, altered taste, and facial numbness suggest the possibility of basal skull neoplasm. We describe a patient, with previously undiscovered fibromuscular dysplasia, who presented with severe neck and face pain, dysgeusia, oculosympathetic paresis, and markedly reduced facial sensation due to a spontaneous vascular dissection. Altered facial sensation should now be included in the symptomatology of internal carotid artery dissection.

Aortic Dissection↗
PubMed1987

Lingual numbness and speech articulation deviation associated with temporomandibular joint disk displacement.

A prospective investigation of 208 patients with painful, arthrographically verified temporomandibular joint disk displacement revealed that seven patients (3%) demonstrated lingual numbness associated with speech articulation impairment. The speech disorder was characterized primarily by a distortion in the production of /s,r,d, and t/. The lingual numbness and the speech disorder had in all cases started in association with a painful onset of permanent displacement of the temporomandibular joint disk. Local anesthetic blocking of the auriculotemporal nerve eliminated both joint pain and muscle pain and normalized tongue sensitivity and speech articulation. Placebo injections of saline solution resulted in no change. The explanation of the phenomenon is that the course of the lingual nerve for these seven patients was through the lateral pterygoid muscle rather than mesial to the muscle bundles and that an arthrokinetic myospasm resulted in compression of the lingual nerve. In order to test the hypothesis that the condition of lingual nerve entrapment in the lateral pterygoid muscle does exist, the course of the nerve was studied at dissection in 52 specimens from 26 cadaver heads. In 49 of the specimens, the lingual nerve descended deep to the lateral pterygoid muscle as has been traditionally defined. However, in three specimens, the nerve passed through the inferior belly of the muscle, revealing the condition of lingual nerve entrapment.

Adult↗
PubMed1992

"Numb, clumsy hands" and tactile agnosia secondary to high cervical spondylotic myelopathy: a clinical and electrophysiological correlation.

Four patients presented with a distinctive syndrome of "numb, clumsy hand" and tactile agnosia. Myelography and computed tomographic myelography (CTM) of the cervical spine documented major spondylotic compressive lesions mainly between the C3 and C5 levels. The cortical responses of dermatomal somatosensory evoked potentials (DSEPs) revealed progressively prolonged peak latencies and progressively decreased amplitudes of early components from C6 to C8 dermatomal stimulation. In comparison, the C5 and L2 DSEPs were affected to a lesser extent. This finding suggests that high cervical cord compression may produce dysfunction of the dorsal column caudal to the direct compressive sites. In other words, the funiculus cuneatus of C6-8 cord is most affected in high cervical myelopathy. Moreover, the funiculus cuneatus is within the border zone susceptible to an overall reduction in blood flow. We conclude therefore, that ischemia secondary to cord compression is the pathophysiology resulting in this unique syndrome of "numb, clumsy hands" and tactile agnosia.

Aged↗
PubMed1992

Herald facial numbness.

Three unusual patients who developed subacute facial numbness as the heralding symptom of an expanding tumor that involved the trigeminal nerve fibers are reported. The first patient had clinical and electrophysiological evidence of an isolated mental neuropathy as a result of metastatic lesions with bone destruction from a renal cell carcinoma. The second patient had a sensorimotor trigeminal neuropathy caused by a direct compression of the semilunar ganglion by a cavernous hemangioma of Meckel's cave. The last patient experienced facial numbness as the unusual presenting manifestation of a primary brainstem lymphoma. Patients 1 and 3 died a few weeks after the admission, whereas patient 2 poorly recovered. Despite the availability of new techniques for early diagnosis, this report demonstrates how difficult it can initially be to differentiate a 'benign' trigeminal neuropathy from serious conditions and underscores the poor prognosis of fifth nerve fibers involvement by an expanding mass. Early referral with clinical and electrophysiological evaluation appears to be of crucial importance.

Adult↗
PubMed1991

[Burkitt's type ALL with numb chin syndrome as an initial manifestation].

A case of Burkitt's type ALL with numb chin syndrome as the initial manifestation is described. A 57-year-old Japanese male was admitted to our hospital in November 14, 1989 because of paresthesia at the chin and lower lip with diplopia and ptosis. Neurological examination revealed oculomotor paralysis of the right side and hypesthesia on the chin, lower lip and buccal mucous membrane. Laboratory findings showed increased leukocyte count. Bone marrow aspirate revealed hypercellular marrow with 92.3% leukemic cells which had vacuoles in the cytoplasm and surface marker of IgM, kappa type. The abnormalities of karyotype included t(8;14). He was treated with chemotherapy and radiation. His conditions were temporarily improved, but relapsed later and died in March 6, 1990. Leukemic infiltrations to the trigeminal nerve were found in autopsy. The relationship between lymphoid malignancies and numb chin syndrome was discussed.

Burkitt Lymphoma↗
PubMed1990

[Surgery cures numbness of the hand. Long-term follow-up of carpal tunnel decompression].

One hundred and ninety-one hands with suspected carpal tunnel syndrome (CTS) were treated with surgical decompression of the median nerve. In a retrospective analysis 2.5-3 years later, an inquiry was carried out by questionnaire and the patients' records were examined to evaluate the final outcome. The questionnaire was answered by all 158 still living patients (ie, 175 hands), of whom 91 per cent reported numbness in the hand to have been completely relieved after surgery, while 23 per cent had had a recurrence of numbness, or other hand problems not clearly related to CTS, though just under half of this 23 per cent reported their symptoms to be milder than prior to operation. Thus, 2.5-3 years after surgical intervention, 85 per cent of the patients had recovered completely or improved; and 96 per cent were satisfied with the outcome. To conclude, surgical treatment of CTS is a technically simple operation with good final results.

Adult↗
PubMed1992

Mental neuropathy (numb chin syndrome). A harbinger of tumor progression or relapse.

The authors report four patients whose initial symptom of tumor recurrence or progression was unilateral numbness of the chin. Two patients had Hodgkin lymphoma, one had malignant melanoma, and one had prostate cancer. Physical examination was notable only for unilateral anesthesia of the chin and lower lip. Diagnostic evaluation, including computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain, plain radiographs of the mandible, and cerebrospinal fluid analysis for protein, glucose, and cytology were normal. Bone scans revealed osseous lesions in the axial skeleton of all patients, whereas only two patients had abnormal uptake in the mandible. The authors conclude that in the setting of a negative evaluation for central nervous system (CNS) or local mandibular disease, mental neuropathy is associated with recurrent or progressive skeletal disease. In addition, to document relapsed or progressive cancer, the skeletal system may have to be examined at sites distant from the mandible.

Adult↗
PubMed1989

Giant aneurysm of the petrous carotid artery presenting with facial numbness.

We present the case of a 56-year-old man who complained of numbness in his cheek, and was shown to have a very large partly thrombosed aneurysm of the ipsilateral petrous carotid artery. The radiological findings and differential diagnosis are discussed. Aneurysm of the petrous carotid should be included in the differential diagnosis of any parasellar mass.

Carotid Artery Diseases↗
PubMed1986

Numbness of half of the tongue.

We report a case of intermittent compression of he lingual nerve due to sialolithiasis and presenting with episodic unilateral numbness of the tongue. Removal of the obstruction has relieved the patient of symptoms over a 21 month period to date.

Adult↗