Common Skin Diseases

Nguyen, Tuyen; Tarapore, Eric; Atwood, Scott X.

doi:10.1002/9783527814633.ch5

Cited by 5 publications

(2 citation statements)

References 116 publications

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“…Aberrant activation of the HH pathway results in uncontrolled proliferation and differentiation that leads to tumorigenesis in various tissues, with medulloblastoma ( 2 , 3 ), rhabdomyosarcoma ( 4 ), and basal cell carcinoma (BCC) ( 5 ) commonly displaying mutations in HH pathway components. BCC is a locally invasive epithelial cancer that represents the most prevalent cancer in the United States, with more than four million cases estimated each year ( 6 ). While most cases of BCC are characterized by low mortality and metastasis that can be easily excised ( 7 ), advanced BCCs display elevated invasiveness, metastasis, and mortality ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation

et al. 2021

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Basal cell carcinoma (BCC) is a locally invasive epithelial cancer that is primarily driven by the Hedgehog (HH) pathway. Advanced BCCs are a critical subset of BCCs that frequently acquire resistance to Smoothened (SMO) inhibitors and identifying pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify a PI3K pathway expression signature in BCC. Pharmacological inhibition of PI3K activity in BCC cells significantly reduces cell proliferation and HH signaling. However, treatment of Ptch1fl/fl; Gli1-CreERT2 mouse BCCs with the PI3K inhibitor BKM120 results in a reduction of tumor cell growth with no significant effect on HH signaling. Downstream PI3K components aPKC and Akt1 showed a reduction in active protein, whereas their substrate, cyclin-dependent kinase inhibitor p21, showed a concomitant increase in protein stability. Our results suggest that PI3K promotes BCC tumor growth by kinase-induced p21 degradation without altering HH signaling.

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Section: Introductionmentioning

confidence: 99%

PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation

et al. 2021

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“…BCCs are locally invasive epithelial tumors that affect approximately 4 million people in the United States annually (Nguyen et al, 2019) Most small early-stage tumors can be surgically removed.…”

Section: Introductionmentioning

confidence: 99%

Isoform-specific aPKC renders primary cilia dispensable for Hedgehog signaling and basal cell carcinoma growth

Nguyen

Jeon

Jhumkhawala

et al. 2020

Preprint

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Primary cilia loss is a common feature of advanced cancers. While primary cilia are necessary to initiate Hedgehog (HH)-driven cancers, how HH pathway activity is maintained in advanced cancers devoid of primary cilia is unclear. Here, we find that HH-driven basal cell carcinoma (BCC) accumulate mutations in the Alström and Usher syndrome genes in advanced and SMO inhibitorresistant tumors. Loss of Alström and Usher syndrome gene expression, which are common underlying causes of deafness and blindness, suppresses ciliogenesis and HH signaling. Atypical protein kinase C iota/lambda (aPKC) is a GLI1 kinase with higher expression in advanced BCCs and we show that a constitutively active isoform drives HH pathway activity and mutually antagonizes primary cilia. Overexpression of the constitutively active aPKC variant can maintain HH pathway activity in the absence of primary cilia and can drive resistance to the SMO antagonist vismodegib regardless of cilia status. Finally, superficial BCCs display less primary cilia and higher aPKC expression, which is inversely correlated in nodular BCC subtypes. Our results suggest aPKC may serve as a biomarker for SMO inhibitor sensitivity and a target for clinical application.

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Right Potency Matters: A Case Report of Homoeopathic Treatment of Verruca Palmaris

Sahoo

Barik

Hati³

et al. 2018

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Warts are caused by human papilloma viruses (HPV) that can affect any part of the body including hands and feet. Verruca palmaris (VP) is a common manifestation due to HPV infection in keratinocytes of the palms. In the conventional system of medicine, VP is commonly managed through cauterisation, cryosurgery, surgical removal or topical ointments, which have many limitations. Scientific documentation for the treatment of VP by homoeopathic medicines is very scanty. In this context, the present case report is of a 40-year-old male patient, who had multiple warts on his right palm for more than 2 years. The patient was treated previously with allopathic medications and external applications, without any significant improvement. Homoeopathic remedy (i.e. Natrum mur) was initially administered in 30C potency for 30 days, but no improvement was observed in the patient. Interestingly, when the potency was increased to 200C, a speedy recovery was observed and the patient was fully cured within 3 months. Therefore, it can be concluded from the case study that VP, when treated on the basis of the totality of symptoms, with an accurately selected remedy in suitable potency results in cure. In this particular case, Natrum mur worked well for warts on the palm. Most importantly, it was observed in this case that the selection of right potency is very essential and it should match correctly with the susceptibility of the patient to result in rapid cure.

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Common Skin Diseases

Cited by 5 publications

References 116 publications

PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation

PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation

Isoform-specific aPKC renders primary cilia dispensable for Hedgehog signaling and basal cell carcinoma growth

Right Potency Matters: A Case Report of Homoeopathic Treatment of Verruca Palmaris

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